Prestige Antibodies® 在乳腺癌研究中的应用

人类蛋白质图谱



proteinatlas.org

人类蛋白质图谱表征人类蛋白质组

在克努特和爱丽丝瓦伦贝里基金会(Knut and Alice Wallenberg Foundation)的资助下,由Mathias Uhlén教授领导的瑞典研究团队于2003年发起了人类蛋白质图谱(Human Protein Atlas,HPA)项目。1,2 这个独一无二的世界领先级项目利用抗体对人类蛋白质组进行了全面系统的探索。

HPA项目旨在绘制完整人类蛋白质组的表达图谱。为实现该目标,研究人员针对所有蛋白质编码人类基因开发了高度特异性的Triple A多克隆抗体,并利用组织阵列技术为大量组织和细胞建立了蛋白质谱图。所采用的应用包括免疫组化(IHC)、Western blot(WB)分析、蛋白质芯片检测和免疫荧光共聚焦显微镜(ICC-IF)。

 

人类蛋白质图谱,2014年11月

2014年11月发布的人类蛋白质图谱第13版公布了完整人类蛋白质组的组织图谱。大量数据被分为四个独立分册:组织图谱(Tissue Atlas)、癌症图谱(Cancer Atlas)、亚细胞图谱(Subcell Atlas)和细胞系图谱(Cell Line Atlas)。组织图谱中所有蛋白质的表达谱是基于针对大量人类组织的IHC分析,该图谱现已囊括与每种基因的RNA测序数据相关的蛋白质表达数据。癌症图谱研究了多种癌症中的差异表达基因,而亚细胞图谱提供了通过共聚焦显微镜获得的亚细胞定位。细胞系图谱包含了关于常见细胞系中蛋白质表达的其他信息,该图谱已成为一款备受欢迎的研究工具。

该项目对来自48种不同正常人类组织、20种不同类型癌症和44个不同人类细胞系的样品进行了组织芯片检测。48种正常组织的样品均重复检测三次,并代表82种不同的细胞类型。所有正常组织图像均对表达水平进行了病理学注释并在正常组织图谱中展示,其提供了关于人类基因在mRNA和蛋白质水平上的表达谱的信息。mRNA表达数据来自于27种主要正常组织类型的RNA深度测序(RNA-Seq)数据。

癌症图谱包含基于大量人类癌症标本中蛋白质表达模式的基因表达数据。利用来自216个不同癌症样本的20种最常见人类癌症类型,针对所有包含的基因进行分析。所有癌症组织图片均经过病理学家手动注释,与正常组织图谱一样,蛋白质数据包括对应于16.621个基因的蛋白质表达水平,因为它们均具有可用抗体。

 

在乳腺组织样本和细胞中进行验证

在正常组织图谱中,每种抗体具有来自三名不同个体的正常乳腺样本的IHC图片。此外,癌症图谱为每种抗体提供了来自多达12名患者的乳腺肿瘤样本(重复2次)的IHC图片,细胞系图谱也为大部分抗体提供了来自MCF-7和SK-BR-3乳腺细胞的图片。

 

参考文献

  1. Uhlén M et al. (2010) Towards a knowledge-based Human Protein Atlas. Nat Biotechnol 28(12):1248–50.
  2. Uhlén et al. (2015) Proteomics. Tissue-based map of the human proteome. Science 23;347(6220).

Prestige Antibodies®由Atlas Antibodies提供技术支持

 

Prestige Antibodies – HPA的基础

Prestige Polyclonals的高度特异性以及与其他蛋白质的低交叉反应性主要基于抗原序列的全面筛选、重组抗原的亲和纯化、多种实验方法验证和严格的审批流程。

 

开发

Prestige Antibodies的抗原是长度约50-150个氨基酸的重组人蛋白表位识别标签(PrESTs)。通过使用专门软件对PrESTs进行设计,使这些蛋白质片段含有与天然蛋白质相同的独特表位,并适合激发高特异性抗体的生成。通过人类全基因组扫描,确保作为抗原的PrESTs与其它人类蛋白质的同源性最低。

 

审批

Prestige Antibodies的审批需综合考量IHC、WB或ICC-IF的实验结果、RNA测序结果以及通过生物信息学预测和参考文献获得的信息。由于文献通常无法判定结论,因此,HPA项目的一个重要目标就是针对同一个蛋白质靶标生产一对无重叠表位的抗体,从而利用这两个抗体相互验证。

 

Prestige Antibodies 产品目录

如今,Prestige Polyclonals的抗体数量已经超过17000个,并且每年新增2,000个抗体。

在人类蛋白质图谱项目中开发和鉴定的抗体,分别被Sigma-Aldrich和Atlas Antibodies公司以Prestige Antibodies和Triple A Polyclonals品牌名称提供给科学界。

 

单克隆抗体开发

Prestige Antibodies还包括一定数量的小鼠单克隆抗体。单克隆抗体产品目录每年随新产品的推出而不断扩增。

 

独特的性质

经过特殊处理的克隆仅能识别独特的无重叠表位和/或同种型。利用与Triple A Polyclonals同样严格的PrEST生产工艺和鉴定流程,使单克隆抗体在获批应用中表现出优异的性能,同时具有明确的特异性、有保证的连续性和稳定的供应。一般来说,这些单克隆抗体可进行高倍数稀释并有助于实现更标准的检测流程。

 

克隆选择

在对选定杂交瘤进行亚克隆和扩增之前,对大量ELISA阳性细胞上清液进行功能鉴定,为每个应用选择最佳克隆。

 

表位定位

使用合成重叠肽微珠阵列法对克隆进行表位定位,选出仅含无重叠表位的克隆。

 

分型

对所有单克隆抗体进行分型,以便使用同种型特异性二抗进行多重检测。

 

杂交瘤细胞培养

Atlas Antibodies在生产扩大阶段利用体外方法进行生产,取代使用小鼠生产腹水液。

 

抗体鉴定

Prestige单克隆抗体的鉴定从广泛的文献检索开始,选出最相关和最具临床意义的组织用于IHC鉴定。通常,IHC应用数据为每个抗体提供一种以上的组织类型。除阳性染色组织外,还会提供阴性对照组织染色以及相关的临床肿瘤组织染色。

Western blot(WB)鉴定包括来自内源性人类细胞或组织蛋白裂解物或重组全长人类蛋白裂解物(可选)的结果。

因此,每个单克隆抗体均附带其特定靶点的最相关的鉴定数据。

所有Prestige Polyclonals的产品编号以“HPA”开头,单克隆抗体以“AMAB”开头。

临床标记物(ESR1、HER2、Ki67、PGR)

成熟的临床乳腺癌标记物

 

货号 Target Protein Product Description Validated Applications
HPA000449
Estrogen receptor Anti-ESR1 IHC,WB
HPA000450 Estrogen receptor Anti-ESR1 IHC,WB
HPA004751 Progesteron receptor Anti-PGR1 IHC,ICC-IF
HPA008428 Progesteron receptor Anti-PGR IHC
HPA017176 Progesteron receptor Anti-PGR IHC
HPA001383 HER2/ERBB2 Anti-ERBB2 IHC,WB
AMAb90627 HER2/ERBB2 Anti-HER2 IHC,WB
HPA000451 Ki67/MKI67 Anti-MKI672 IHC,ICC-IF
HPA001164 Ki67/MKI67 Anti-MKI673 IHC,ICC-IF
AMAb90870 Ki67/MKI67 Anti-MKI67 IHC
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HER2/ERBB2

使用HER2抗体(AMAb90627)对人类乳腺肿瘤进行免疫组化染色,结果显示HER2阳性导管癌肿瘤细胞呈强细胞膜阳性(结合中度的细胞质阳性),而HER2阴性导管癌肿瘤细胞无细胞膜阳性。通过Western Blot分析,在乳腺癌细胞SK-BR-3中检测到HER2。

 

孕激素受体

使用PGR抗体(HPA004751)对正常人类宫体(子宫)组织进行IHC染色,结果显示腺细胞呈强细胞核阳性。在提供的乳腺癌样品中,肿瘤细胞染色结果也显示细胞核阳性。ICC-IF结果显示U-251MG细胞核被染色。

 

雌激素受体

使用 ESR1抗体(HPA000449)进行IHC染色,结果显示人乳腺组织中的腺细胞和乳腺癌样品中的肿瘤细胞均呈现明显的细胞核阳性。

 

使用ESR1抗体(HPA000450)进行IHC染色,结果显示人宫体组织中的腺细胞和基质细胞以及乳腺癌样品中的肿瘤细胞均呈强细胞核阳性。

 

Ki67

使用MKI67抗体(HPA000451)进行IHC染色,结果显示人淋巴结反应中心的部分细胞呈强细胞核阳性。在乳腺癌中,肿瘤细胞的ICC-IF染色结果也显示细胞核阳性,人U-2OS细胞染色显示核仁阳性。

 

使用MKI67抗体(HPA001164)对人扁桃体组织进行IHC染色,结果显示反应中心细胞的细胞核被染色。在乳腺癌的肿瘤细胞中,染色主要发生于细胞核,而U-2OS细胞的ICC-IF染色结果显示核仁呈强阳性。

 

使用单克隆MKI67抗体(AMAb90870)对人结肠淋巴结进行IHC染色,结果显示反应中心细胞呈强细胞核和核仁免疫反应性。子宫组织染色显示部分腺细胞呈细胞核阳性。

乳腺癌研究使用的抗体

本节所述抗体是根据参考文献或与相应靶蛋白的乳腺癌相关性进行选择的。

 

BRCA1

使用BRCA1抗体(HPA034966)进行IHC染色,结果显示正常人乳腺组织中的腺细胞和乳腺癌样品中的肿瘤细胞呈阳性。

 

使用BRCA2抗体(HPA026815)对正常人乳腺组织进行IHC染色,结果显示腺细胞呈阳性。在乳腺癌样品中,肿瘤细胞呈细胞核染色阳性。

 

ACAT1

使用ACAT1抗体(HPA004428)对人肝脏组织进行免疫组化染色,结果显示肝细胞呈强细胞质阳性。通过Western Blot分析,在人类细胞RT-4和U251-MG以及肝脏和扁桃体组织裂解物中检测到ACAT1。人类细胞A-431的ICC-IF染色结果显示线粒体呈阳性。

 

CD44

使用CD44抗体(HPA005785)对人食道组织进行免疫组化染色,结果显示鳞状上皮细胞呈强细胞质和细胞膜阳性。通过Western Blot分析,在人类细胞U-251MG中检测到CD44。人类细胞U-251MG的ICC-IF染色结果显示细胞膜呈阳性。

 

Cat. No. Target Protein Product Description Validated Applications
HPA008788 53BP1 Anti-TP53BP1 IHC,ICC-IF
HPA022133 53BP1 Anti-TP53BP1 IHC,WB*,ICC-IF
HPA004428 ACAT1 Anti-ACAT11,2 IHC,WB*,ICC-IF
HPA007569 ACAT1 Anti-ACAT12-4 IHC,WB,ICC-IF
HPA007912 AGR2 Anti-AGR25 IHC,WB
HPA024210 AIB1/NCOA3 Anti-NCOA3 IHC,ICC-IF
AMAb90660 Anillin/ANLN Anti-ANLN IHC,WB
AMAb90662 Anillin/ANLN Anti-ANLN IHC,WB
HPA005680 Anillin/ANLN Anti-ANLN6 IHC,WB,ICC-IF
HPA024006 ARG1 Anti-ARG17 IHC,WB
HPA005468 ASAH1 Anti-ASAH18,9 IHC,WB
HPA028264 ATR Anti-ATR IHC
HPA029455 BAAT1/BRAT1 Anti-BRAT1 IHC,WB
HPA003175 BACH1 Anti-BACH110 IHC,WB,ICC-IF
HPA028814 BAP1 Anti-BAP1 IHC,WB,ICC-IF
HPA044864 BARD1 Anti-BARD1 IHC,ICC-IF
HPA029159 Beta-Catenin Anti-CTNNB1 IHC,WB*,ICC-IF
HPA029160 Beta-Catenin Anti-CTNNB1 IHC, IF
HPA002317 BIRC3/API2 Anti-BIRC311 IHC,WB,ICC-IF
HPA012897 BIT1/ PTRH2 Anti-PTRH212,13 IHC,WB,ICC-IF
HPA005689 Blooms Syndrome Prot Anti-BLM IHC,ICC-IF
HPA030472 Bmi1 Anti-BMI1 IHC,WB*,ICC-IF
HPA034966 BRCA1 Anti-BRCA1 IHC
HPA026815 BRCA2 Anti-BRCA2 IHC,ICC-IF
HPA005474 BRIP1/FANCJ Anti-BRIP1 IHC,WB,ICC-IF
HPA036596 C11orf51/ANAPC15 Anti-ANAPC15 IHC,WB,ICC-IF
HPA051365 CAR/NR1I3 Anti-NR1I3 IHC,ICC-IF
HPA001302 CASP8 Anti-CASP8 IHC,WB,ICC-IF
HPA005688 CASP8 Anti-CASP8 IHC,WB,ICC-IF
HPA008773 CAXII/CA12 Anti-CA1214-17 IHC,WB
HPA005785 CD44 Anti-CD4418-22 IHC,WB,ICC-IF
HPA028900 CD82 Anti-CD82 IHC,WB
HPA004812 CDH1 Anti-CDH1 IHC,ICC-IF
HPA019758 CEA/CEACAM5 Anti-CEACAM5 IHC,WB
HPA001878 CHEK2 Anti-CHEK2 IHC,WB
HPA001254 CKB Anti-CKB IHC
HPA004135 CRABP2 Anti-CRABP2 IHC,WB,ICC-IF
HPA015955 CTNND1 Anti-CTNND1 IHC,WB*,ICC-IF
HPA010663 CX32/GJB1 Anti-GJB123 IHC,WB
HPA018169 Cyclin E1 Anti-CCNE1 IHC,WB,ICC-IF
HPA020626 Cyklin A2 Anti-CCNA2 IHC,WB
HPA023040 Cytokeratin 14/CK14 Anti-KRT14 IHC,WB*,ICC-IF
HPA000452 Cytokeratin 17/CK17 Anti-KRT1724 IHC,WB
HPA000453 Cytokeratin 17/CK17 Anti-KRT17 IHC,WB,ICC-IF
HPA000258 DACH2 Anti-DACH225 IHC,ICC-IF
HPA019907 DBC1/KIAA1967 Anti-KIAA1967 IHC,WB*,ICC-IF
HPA019943 DBC1/KIAA1967 Anti-KIAA1967 IHC,ICC-IF
HPA022962 DCAF7 Anti-DCAF726 IHC, WB
HPA003315 Decorin/DCN Anti-DCN27,28 IHC, WB
HPA028483 DIRAS3 Anti-DIRAS3 IHC,WB
HPA028557 DIRAS3 Anti-DIRAS3 IHC,WB
HPA029384 DIRAS3 Anti-DIRAS3 IHC
AMAb90816 EGFR Anti-EGFR IHC,WB
AMAb90819 EGFR Anti-EGFR WB
HPA001200 EGFR Anti-EGFR29 IHC
HPA018530 EGFR Anti-EGFR30 IHC,WB,ICC-IF
HPA003901 Endoplasmin/ HSP90B1 Anti-HSP90B127,31 IHC,WB,ICC-IF
HPA002025 ERLIN2 Anti-ERLIN232,33 IHC,WB*,ICC-IF
HPA026676 ERFF/C1orf64 Anti-C1orf6434 IHC,WB,ICC-IF
HPA007425 FAAH Anti-FAAH35 IHC,ICC-IF
HPA035305 FGFR2 Anti-FGRF2 IHC,WB,ICC-IF
HPA029731 GATA3 Anti-GATA3 IHC, WB
HPA009177 GCDFP/PIP Anti-PIP IHC,WB
HPA017046 GEF-H1 Anti-ARHGEF236,37 IHC,WB
HPA025226 GGH Anti-GGH35 IHC,WB
HPA008763 Granulin Anti-GRN38 IHC,ICC-IF, WB
HPA028747 Granulin Anti-GRN38 IHC,ICC-IF
HPA001275 HIF-1 alpha/HIF1A Anti-HIF1A39-42 IHC,ICC-IF
HPA008436 HJURP Anti-HJURP43-45 IHC,WB,ICC-IF
HPA004727 HMGCL Anti-HMGCL2 IHC,WB
HPA008338 HMGCR Anti-HMGCR46 IHC
HPA021467 HSD17B14 Anti-HSD17B14 IHC,WB,ICC-IF
HPA000764 KLK3/PSA Anti-KLK347,48 IHC
HPA019693 LSP1 Anti-LSP1 IHC,WB,ICC-IF
HPA001939 MMP2 Anti-MMP2 IHC
HPA004179 MUC1/CA15-3 Anti-MUC1 IHC,WB
HPA007235 MUC1/CA15-3 Anti-MUC1 IHC
HPA008855 MUC1/CA15-3 Anti-MUC1 IHC,ICC-IF
HPA001429 NBN Anti-NBN IHC,WB,ICC-IF
HPA030278 NRP1 Anti-NRP1 IHC
HPA029814 Oncostatin M Anti-OSM49 IHC,WB
AMAb90956 P53 Anti-P53 IHC,WB
HPA021241 PHGDH Anti-PHGDH50-52 IHC,WB*,ICC-IF
HPA031314 PGD Anti-PGD IHC,WB*
HPA006563 PKC alpha/PKCA Anti-PKCA IHC,WB*,ICC-IF
HPA006564 PKC alpha/PKCA Anti-PKCA IHC,WB*,ICC-IF
HPA003412 PLAT Anti-PLAT IHC,WB,ICC-IF
HPA006366 POLRMT Anti-POLRMT53 IHC
HPA020376 PSPH Anti-PSPH50 IHC,WB
HPA047183 PTMA Anti-PTMA IHC,ICC-IF
HPA008890 PTTG1 Anti-PTTG1 IHC,ICC-IF
HPA037503 RAP80/UIMC1 Anti-UIMC1 IHC,WB
HPA037504 RAP80/UIMC1 Anti-UIMC1 IHC,WB,ICC-IF
HPA006079 REST Anti-REST54,55 IHC,ICC-IF
HPA003624 RBM3 Anti-RBM356,57 IHC,WB*,ICC-IF
AMAb90655 RBM3 Anti-RBM358-65 IHC,WB
HPA009026 RRBP1 Anti-RRBP166 IHC,ICC-IF, WB
HPA035857 rs4973768/SLC4A7 Anti-SLC4A7 IHC
HPA001893 SIX1 Anti-SIX167-74 IHC,WB,ICC-IF
AMAb90544 SIX1 Anti-SIX1 IHC,WB
HPA014404 SNCG Anti-SNCG IHC,WB
HPA017254 STK11 Anti-STK11 IHC,WB,ICC-IF
HPA002830 SURVIvin/BIRC5 Anti-BIRC5 IHC,WB,ICC-IF
HPA000500 T-STAR/KHDRBS3 Anti-KHDRBS375,76 IHC,WB
HPA004823 Tenascin C/TNC Anti-TNC77-79 IHC,WB
HPA003425 TFF1 Anti-TFF180-82 IHC,WB
HPA002982 THBD Anti-THBD IHC,WB
HPA019881 THEM2/ACOT13 Anti-ACOT13 IHC,WB*,ICC-IF
HPA006458 TOP2A Anti-TOP2A IHC,WB,ICC-IF
HPA026773 TOP2A Anti-TOP2A IHC,ICC-IF
HPA014405 UGT8 Anti-UGT883 IHC,ICC-IF
HPA007547 ULBP1 Anti-ULBP184 IHC
HPA023930 ZNF703 Anti-ZNF70332 IHC,ICC-IF

* 对人类和啮齿动物样本均进行WB分析

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  23. Teleki I et al. The potential prognostic value of connexin 26 and 46 expression in neoadjuvant-treated breast cancer. BMC Cancer 1350. Epub 2013/02/02.
  24. Kiflemariam S et al. Scalable in situ hybridization on tissue arrays for validation of novel cancer and tissue-specific biomarkers. PLoS One 2012;7(3):e32927.
  25. Nodin B et al. Discovery of dachshund 2 protein as a novel biomarker of poor prognosis in epithelial ovarian cancer. J Ovarian Res 2012 Jan 27;5(1):6.
  26. Sircoulomb F et al. ZNF703 gene amplification at 8p12 specifies luminal B breast cancer. EMBO Mol Med 2011 Mar; 3(3):153–166. Epub 2011 Feb 15.
  27. Cawthorn TR et al.Proteomic Analyses Reveal High Expression of Decorin and Endoplasmin (HSP90B1) Are Associated with Breast Cancer Metastasis and Decreased Survival. PLoS One 2012;7(2):e30992.
  28. Henke A et al. Stromal Expression of Decorin, Semaphorin6D, SPARC, Sprouty1 and Tsukushi in Developing Prostate and Decreased Levels of Decorin in Prostate Cancer. PLoS One 7(8):e42516. Epub 2012 Aug 3.
  29. Hudson EP et al. Multiplex epitope mapping using bacterial surface display reveals both linear and conformational epitopes. Sci Rep 2012;2:706.
  30. Arabi A et al. Proteomic screen reveals Fbw7 as a modulator of the NF-κB pathway. Nat Commun 2012;3:976.
  31. Ito A et al. Novel application for pseudopodia proteomics using excimer laser ablation and two-dimensional difference gel electrophoresis. Lab Invest 2012 Sep;92(9):1374–85.
  32. Holland DG et al. ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium. EMBO Mol Med 2011 Mar;3(3):167–80.
  33. Mulder J et al. Tissue profiling of the mammalian central nervous system using human antibody-based proteomics. Mol Cell Proteomics 2009 Jul;8(7):1612–22.
  34. Su D et al. Role of ERRF, a Novel ER-Related Nuclear Factor, in the Growth Control of ER-Positive Human Breast Cancer Cells. Am J Pathol 2012 Mar; 180(3):1189–1201.
  35. Shubbar E et al. High levels of γ-glutamyl hydrolase (GGH) are associated with poor prognosis and unfavorable clinical outcomes in invasive breast cancer. BMC Cancer 2013 Feb 1;13:47.
  36. Liao YC et al. Overexpressed hPTTG1 promotes breast cancer cell invasion and metastasis by regulating GEF-H1/RhoA signalling. Oncogene 2012 Jun 21;31(25):3086–97
  37. Cheng IK et al. GEF-H1 over-expression in hepatocellular carcinoma promotes cell motility via activation of RhoA signalling. Pathol 2012 Jul 30.
  38. Elkabets M et al. Human tumors instigate granulin-expressing hematopoietic cells that promote malignancy by activating stromal fibroblasts in mice. J Clin Invest 2011 Feb 1;121(2):784–99.
  39. Zibert JR et al. Halting angiogenesis by non-viral somatic gene therapy alleviates psoriasis and murine psoriasiform skin lesions. J Clin Invest 2011 Jan 4;121(1):410–21.
  40. Smyth LG et al. Carbonic anhydrase IX expression in prostate cancer. Prostate Cancer and Prostatic Diseases 2009 Dec;13(2):178–181.
  41. Paatero I et al. Interaction with ErbB4 promotes hypoxia-inducible factor-1α signaling. J Biol Chem 2012 Mar 23;287(13):9659–71.
  42. Zbytek B et al. Putative role of HIF transcriptional activity in melanocytes and melanoma biology. Dermatoendocrinol 2013 Apr 1; 5(2):239–251. Epub 2013/04/01.
  43. Hu Z et al. The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer. Breast Cancer Res 2010;12(2):R18.
  44. Shuaib M et al. HJURP binds CENP-A via a highly conserved N-terminal domain and mediates its deposition at centromeres. Proc Natl Acad Sci U S A 2010 Jan 26;107(4):1349–54.
  45. de Tayrac M et al. Prognostic Significance of EDN/RB, HJURP, p60/CAF-1 and PDLI4, Four New Markers in High-Grade Gliomas. PLoS One 2013 Sep 11;8(9):e73332. 46. Bjarnadottir O et al. Targeting HMG-CoA reductase with statins in a window-ofopportunity breast cancer trial. Breast Cancer Res Treat 2013 Apr;138(2):499–508.
  46. Bjarnadottir O et al. Targeting HMG-CoA reductase with statins in a window-ofopportunity breast cancer trial. Breast Cancer Res Treat 2013 Apr;138(2):499–508.
  47. Jaraj SJ et al. GAD1 is a biomarker for benign and malignant prostatic tissue. Scand J Urol Nephrol 2011 Feb;45(1):39–45.
  48. Liu H et al. Single-cell clones of liver cancer stem cells have the potential of differentiating into different types of tumor cells. Cell Death Dis 2013 Oct; 4(10):e857-. Epub 2013/10/17.
  49. Guo L et al. Stat3-coordinated Lin-28-let-7-HMGA2 and miR-200-ZEB1 circuits initiate and maintain oncostatin M-driven epithelial-mesenchymal transition. Oncogene 2013 Nov 7;32(45):5272–82.
  50. Possemato R et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 2011 Aug 18;476(7360):346–50.
  51. Maddocks OD et al. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature 2013 Jan 24;493(7433):542–6.
  52. Nilsson LM et al. Mouse genetics suggests cell-context dependency for Myc-regulated metabolic enzymes during tumorigenesis. PLoS Genet 2012;8(3):e1002573.
  53. Salem AF et al. Mitochondrial biogenesis in epithelial cancer cells promotes breast cancer tumor growth and confers autophagy resistance. Cell Cycle 2012 Nov 15; 11(22):4174–4180.
  54. Wagoner MP et al. The transcription factor REST is lost in aggressive breast cancer. PLoS Genet 2010 Jun 10;6(6):e1000979.
  55. Prada I et al. REST/NRSF governs the expression of dense-core vesicle gliosecretion in astrocytes. J Cell Biol 2011 May 2;193(3):537–49.
  56. Jögi A et al. Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer. Mod Pathol 2009 Dec;22(12):1564–74.
  57. Hjelm B et al. High nuclear RBM3 expression is associated with an improved prognosis in colorectal cancer. Proteomics Clin Appl 2011 Dec;5(11-12):624–35.
  58. Ehlén A et al. Expression of the RNA-binding protein RBM3 is associated with a favourable prognosis and cisplatin sensitivity in epithelial ovarian cancer. J Transl Med 2010 Aug 20;8:78.
  59. Jonsson L et al. High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression. Diagn Pathol 2011 Sep 28;6:9.
  60. Nodin B et al. High MCM3 expression is an independent biomarker of poor prognosis and correlates with reduced RBM3 expression in a prospective cohort of malignant melanoma. Diagn Pathol 782. Epub 2012 Jul 17.
  61. Jonsson L et al. Low RBM3 protein expression correlates with tumour progression and poor prognosis in malignant melanoma: an analysis of 215 cases from the Malmö Diet and Cancer Study. J Transl Med 2011 Jul 21;9:114.
  62. Ehlén Å et al. RBM3-regulated genes promote DNA integrity and affect clinical outcome in epithelial ovarian cancer. Transl Oncol 2011 Aug;4(4):212–21.
  63. Hjelm B et al. High nuclear RBM3 expression is associated with an improved prognosis in colorectal cancer. Proteomics Clin Appl 2011 Dec;5(11-12):624–35.
  64. Boman K et al. Decreased expression of RNA-binding motif protein 3 correlates with tumour progression and poor prognosis in urothelial bladder cancer. BMC Urol 2013 Apr 8;13:17.
  65. Nodin B et al. High MCM3 expression is an independent biomarker of poor prognosis and correlates with reduced RBM3 expression in a prospective cohort of malignant melanoma. Diagn Pathol 2012 Jul 17;7:82.
  66. Telikicherla D et al. Overexpression of ribosome binding protein 1 (RRBP1) in breast cancer. Clin Proteomics 9(1):7. Epub 2012 Jun 18.
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  72. Farabaugh et al. Eya2 is required to mediate the pro-metastatic functions of Six1 via the induction of TGF-β signaling, epithelial-mesenchymal transition, and cancer stem cell properties. Oncogene 2012 Feb 2;31(5):552–62.
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MammaPrint、Oncotype、EndoPredict和uPA检测中基因产物的抗体

本节介绍了Prestige Antibody产品目录中靶向诊断性MammaPrint、Oncotype、EndoPredict和uPA检测所含基因产物的抗体。MammaPrint是一项基因表达谱测试,基于Agendia 公司推出的Amsterdam 70-基因乳腺癌基因标记检测。该测试可评估乳腺癌向身体其他部位转移的风险。MammaPrint的目标是将患者分为“低风险”和“高风险”类别。Oncotype DX(由Genomic Health开发)是美国临床实践中最常用的基因表达谱分析方法,它能够检测肿瘤中的21个基因并确定复发分数(Recurrence Score)。

 

BIRC5/Survivin

使用CD68抗体(HPA048982)对人肺组织进行IHC染色,结果显示巨噬细胞和造血组织(如脾脏)呈强细胞质阳性。

 

CD68/巨噬唾液酸蛋白

使用CD68抗体(HPA048982)对人肺组织进行IHC染色,结果显示巨噬细胞和造血组织(如脾脏)呈强细胞质阳性。


DTL

使用DTL抗体(HPA028016)对人骨髓进行IHC染色,结果显示骨髓细胞呈强细胞核阳性。通过ICC-IF染色,检测到U-251 MG细胞的细胞核被染色。

 

GSTM5

使用GSTM5抗体(HPA048652)进行IHC染色,结果显示人直肠腺细胞呈细胞质阳性;同时,通过WB分析,在RT-4和U-251 MG细胞裂解物以及肝脏组织裂解物中检测到预期大小的条带。

Product No. Target Protein Product Description Validated Applications
HPA002636 AURKA/STK15 Anti-AURKA IHC,WB
HPA012582 AZGP1 Anti-AZGP1 IHC,WB
HPA018121 BAG1 Anti-BAG1 IHC,ICC-IF
HPA002830 BIRC5/Survivin Anti-BIRC5 IHC,WB,ICC-IF
HPA048982 CD68/Macrosialin Anti-CD68 IHC
HPA005565 CDCA7 Anti-CDCA71,2 IHC,WB,ICC-IF
HPA006871 CMC2/C16orf61 Anti-CMC2 IHC
HPA044280 DHCR7 Anti-DHCR7 IHC,WB
HPA018670 DHX58/LGP2 Anti-DHX58 IHC,WB,ICC-IF
HPA019570 DHX58/LGP2 Anti-DHX58 IHC
HPA032152 DIAPH3 Anti-DIAPH3 IHC,WB*
HPA028016 DTL Anti-DTL3 IHC,WB,ICC-IF
HPA022130 ECI2/PECI Anti-ECI2 IHC,WB,ICC-IF
HPA022129 EGLN1/PHD2 Anti-EGLN14 IHC,ICC-IF
HPA036660 ESM1 Anti-ESM1 IHC,WB
HPA000449 Estrogen receptor Anti-ESR1 IHC,WB
HPA000450 Estrogen receptor Anti-ESR1 IHC,WB
HPA044394 Exostosin-1 Anti-EXT1 IHC,WB
HPA018795 FGF18 Anti-FGF18 IHC,WB,ICC-IF
HPA050682 GMPS Anti-GMPS IHC
HPA003011 GNAZ Anti-GNAZ IHC,WB
HPA017346 GPR126/VIGR Anti-GPR126 IHC
HPA047250 GPR180 Anti-GPR180 IHC,ICC-IF
HPA035190 GSTM3 Anti-GSTM3 IHC,WB
HPA048652 GSTM5/GSTM1 Anti-GSTM5 IHC,WB
HPA001383 HER2/ERBB2 Anti-ERBB2 IHC,WB
AMAb90627 HER2/ERBB2 Anti-HER2 IHC,WB
HPA051179 HRASLS Anti-HRASLS IHC
HPA010558 IL6ST/GP130 Anti-IL6ST5 IHC
HPA012114 JHDM1D/KDM7A Anti-JHDM1D IHC,ICC-IF

* 对人类和啮齿动物样本均进行WB分析

  1. Gill RM et al. The MYC-Associated Protein CDCA7 Is Phosphorylated by AKT To Regulate MYC-Dependent Apoptosis and Transformation. Mol Cell Biol 2013 Feb; 33(3):498–513.
  2. Shubbar E et al. Elevated cyclin B2 expression in invasive breast carcinoma is associated with unfavorable clinical outcome. BMC Cancer 131. Epub 2013/01/02.
  3. Karaayvaz M et al. Prognostic significance of miR-215 in colon cancer. Clin Colorectal Cancer 2011 Dec;10(4):340–7.
  4. Bozóky B et al. Novel signatures of cancer-associated fibroblasts. Int J Cancer 2013 Jan 15.
  5. Rognum IJ et al. Interleukin-6 and the serotonergic system of the medulla oblongata in the sudden infant death syndrome. Acta Neuropathol 2009 Oct;118(4):519–3. S Alterations in Breast Cancer from Women Treated with Neoadjuvant Chemotherapy. PLoS One 2013;8(3):e60576.

MMP9

使用MMP9抗体(HPA001238)对人肺组织进行IHC染色,结果显示骨髓组织中的巨噬细胞和骨髓细胞呈强细胞核阳性。

 

使用单克隆MMP9抗体染色,结果显示十二指肠(AMAb90805)和人扁桃体组织(AMAb90804)中的部分淋巴细胞显示强细胞质阳性。

 

LYRIC/MTDH

使用MTDH抗体(HPA010932)进行IHC染色,结果显示人大脑皮层组织中的神经元细胞呈细胞质阳性。对A-431细胞的ICC-IF染色结果显示,内质网被抗体染色。

 

使用单克隆MTDH抗体(AMAb90762)进行IHC染色,结果显示乳腺和结直肠癌样品中的肿瘤细胞呈强细胞质反应性。

 

P5C脱氢酶/ALDH4A1

使用ALDH4A1抗体(HPA006401)进行IHC染色,结果显示人肾脏和肝脏组织呈强细胞质阳性并具有颗粒性。

Product No. Target Protein Product Description Validated Applications
HPA000451 Ki67/MKI67 Anti-MKI671 IHC,ICC-IF
HPA001164 KI67/MKI67 Anti-MKI672 IHC,ICC-IF
AMAb90870 KI67/MKI67 Anti-MKI67 IHC
HPA030241 LIN9 Anti-LIN9 IHC,ICC-IF
HPA012501 LPCAT/AYTL2 Anti-LPCAT1 IHC,WB
HPA022268 LPCAT/AYTL2 Anti-LPCAT13 IHC,WB,ICC-IF
HPA015104 LYRIC Anti-MTDH4 IHC,WB,ICC-IF
HPA010932 LYRIC Anti-MTDH5 IHC,WB*,ICC-IF
AMAb90762 LYRIC Anti-MTDH IHC,WB
AMAb90763 LYRIC Anti-MTDH IHC,WB
HPA013949 Matrix Gla protein Anti-MGP6 IHC
HPA004818 MCM6 Anti-MCM6 IHC,WB*,ICC-IF
HPA017214 MELK/PK38 Anti-MELK IHC,ICC-IF
HPA001238 MMP9 Anti-MMP9 IHC,WB,ICC-IF
AMAb90804 MMP9 Anti-MMP9 IHC,WB
AMAb90805 MMP9 Anti-MMP9 IHC,WB
AMAb90806 MMP9 Anti-MMP9 IHC
HPA017418 MS4A7 Anti-MS4A7 IHC,WB
HPA030530 MYBL2 Anti-MYBL2 IHC,WB
HPA025926 Neuromedin-U Anti-NMU IHC,WB
HPA042904 NUSAP1 Anti-NUSAP1 IHC,ICC-IF
HPA006401 P5C dehydrogenase Anti-ALDH4A1 IHC,WB

* 对人类和啮齿动物样本均进行WB分析

  1. Pohler E et al. Haploinsufficiency for AAGAB causes clinically heterogeneous forms of punctate palmoplantar keratoderma. Nat Genet 2012 Oct 14;44(11):1272–6.
  2. Roca H et al. IL-4 induces proliferation in prostate cancer PC3 cells under nutrient-depletion stress through the activation of the JNK-pathway and survivin upregulation. J Cell Biochem 2012 May; 113(5):1569–1580.
  3. Friedman JS et al. Loss of lysophosphatidylcholine acyltransferase 1 leads to photoreceptor degeneration in rd11 mice. Proc Natl Acad Sci U S A 2010 Aug 31;107(35):15523–8.
  4. Nohata N et al. Tumor suppressive microRNA-375 regulates oncogene AEG-1/ MTDH in head and neck squamous cell carcinoma (HNSCC). J Hum Genet 2011 Aug;56(8):595–601.
  5. Liu B et al. Astrocyte elevated gene-1 regulates osteosarcoma cell invasion and chemoresistance via endothelin-1/endothelin A receptor signaling. Oncol Lett 2013 Feb;5(2):505–510.
  6. Lorenzen JM et al. Fetuin, matrix-Gla protein and osteopontin in calcification of renal allografts. PLoS One 2012;7(12):e52039.

PITRM1/MP1

使用PITRM1抗体(HPA006753)进行IHC染色,结果显示人心肌细胞呈强细胞质阳性。人类细胞U-251 MG的ICC-IF染色结果显示线粒体呈阳性。

 

PRC1

使用PRC1抗体(HPA034521)对人睾丸组织进行IHC染色,结果显示输精管的细胞呈强细胞核阳性。A-431细胞的ICC-IF染色显示细胞核、细胞膜和微管被染色。

 

SCOT/OXCT1

使用OXCT1抗体(HPA012047)对人心肌和肾脏进行IHC染色,结果显示心肌细胞和肾小管细胞分别呈强细胞质阳性。A-431细胞的ICC-IF染色显示线粒体被染色。

 

Product No. Target Protein Product Description Validated Applications
HPA006753 PITRM1/MP1 Anti-PITRM1 IHC,WB,ICC-IF
HPA006754 PITRM1/MP1 Anti-PITRM1 IHC,WB*,ICC-IF
HPA008719 PLAU/UPA Anti-PLAU IHC,WB
HPA034521 PRC1 Anti-PRC1 IHC,ICC-IF
HPA004751 Progesteron receptor Anti-PGR1 IHC,ICC-IF
HPA008428 Progesteron receptor Anti-PGR IHC
HPA017176 Progesteron receptor Anti-PGR IHC
HPA012716 QSOX2/QSCN6L1 Anti-QSOX2 IHC,WB,ICC-IF
HPA039890 RBBP8 Anti-RBBP8 IHC, WB
HPA029970 RECQL5 Anti-RECQL5 IHC,ICC-IF
HPA029971 RECQL5 Anti-RECQL5 IHC,WB,ICC-IF
HPA044428 RTN4RL1/NgR3 Anti-RTN4RL1 IHC
HPA023726 RUNDC1 Anti-RUNDC1 IHC,WB,ICC-IF
HPA006353 SCUBE2/CEGP1 Anti-SCUBE2 IHC,ICC-IF
HPA029871 SCUBE2/CEGP1 Anti-SCUBE2 IHC
HPA012047 SCOT/OXCT1 Anti-OXCT12 IHC,WB*,ICC-IF
HPA050039 SERPINE1/PAI1 Anti-SERPINE1 IHC
HPA006539 SLC2A3/GLUT3 Anti-SLC2A3 IHC
HPA045372 Stanniocalcin-2 Anti-STC2 IHC, WB, IF
HPA015820 STK32B Anti-STK32B IHC,ICC-IF
HPA027923 TGFB3 Anti-TGFB3 IHC,WB
HPA045213 TMEM74B/C20orf46 Anti-TMEM74B IHC
HPA031347 TSPYL5 Anti-TSPYL5 IHC
HPA005908 UCHL5 Anti-UCHL5 IHC,ICC-IF
HPA014290 VEGFR-1 Anti-FLT1 IHC,ICC-IF
AMAb90703 VEGFR-1 Anti-FLT1 IHC
AMAb90704 VEGFR-1 Anti-FLT1 IHC,WB
HPA007121 WISP1 Anti-WISP1 IHC,ICC-IF

* 对人类和啮齿动物样本均进行WB分析

  1. Pereira CB et al. Prognostic and Predictive Significance of MYC and KRAS Alterations in Breast Cancer from Women Treated with Neoadjuvant Chemotherapy. PLoS One 2013;8(3):e60576.
  2. Chang HT et al. Ketolytic and glycolytic enzymatic expression profiles in malignant gliomas: implication for ketogenic diet therapy. Nutr Metab (Lond) 1047. Epub 2013/07/05.
  3. Zibert JR et al. Halting angiogenesis by non-viral somatic gene therapy alleviates psoriasis and murine psoriasiform skin lesions. J Clin Invest 2011 Jan 4;121(1):410–21.

在人类蛋白图谱中鉴定的抗体

在乳腺癌样本中展现出差异的IHC染色模式

采用抗KLHL26抗体(HPA023074)进行IHC分析的结果表明在不同病人的乳腺癌样本中具有不同的膜或胞浆染色模式

抗ACSF2抗体(HPA024693)表明在不同病人的乳腺癌细胞中具有颗粒蛋白胞浆阳性,并从强至阴性

抗GCM1抗体(HPA011343)表明在乳腺癌细胞中具有膜阳性但在正常乳腺组织中为阴性

 

抗AGR3抗体(HPA053942)表明在11/12例乳腺癌病人中具有强的胞浆阳性而1例病人是完全的阴性

货号 Product Description Validated Applications
HPA037918 Anti-AAMDC IHC,WB
HPA037919 Anti-AAMDC IHC
HPA040312 Anti-ABCG4 IHC,ICC-IF
HPA007695 Anti-NIM1 IHC,WB,ICC-IF
HPA023993 Anti-AC145676.2 IHC,WB
HPA024693 Anti-ACSF2 IHC,WB
HPA042014 Anti-ADAMTS13 IHC,WB
HPA053942 Anti-AGR3 IHC
HPA020522 Anti-AIF1L IHC,WB
HPA006171 Anti-AJUBA IHC, WB
HPA046271 Anti-ALDH1A3 IHC,WB
HPA013758 Anti-ANKRD46 IHC,WB
HPA004341 Anti-ASB6 IHC,WB,ICC-IF
HPA005935 Anti-ATF6 IHC
HPA008147 Anti-ATP6V1B2 IHC,WB*,ICC-IF
HPA046678 Anti-AVPR2 IHC
HPA020274 Anti-BCL9 IHC
HPA038478 Anti-BTG4 IHC
HPA026810 Anti-ADIRF IHC,WB
HPA007968 Anti-C10orf54 IHC,WB,ICC-IF
HPA039713 Anti-C12orf76 IHC,WB
HPA008959 Anti-C17orf85 IHC
HPA045811 Anti-C1ORF195 IHC,ICC-IF
HPA051143 Anti-C2orf68 IHC
HPA037889 Anti-SIMC1 IHC,WB
HPA021480 Anti-CAPN8 IHC,WB
HPA023457 Anti-CCDC144NL IHC,WB
HPA027185 Anti-CCDC170 IHC,WB
HPA027121 Anti-CCDC170 IHC,WB
HPA002637 Anti-CDK6 IHC,WB*,ICC-IF
HPA014361 Anti-CLDN3 IHC
HPA041132 Anti-CPNE2 IHC,WB
HPA004135 Anti-CRABP2 IHC,WB,ICC-IF
HPA015077 Anti-CTNND2 IHC
HPA006128 Anti-CXorf67 IHC,WB
HPA017661 Anti-CYP4X1 IHC
HPA012672 Anti-DACH1 IHC,ICC-IF
HPA051589 Anti-DBF4 IHC
HPA050246 Anti-DCHS1 IHC
HPA015655 Anti-DCLK1 IHC
HPA047631 Anti-DECR2 IHC
HPA046708 Anti-DOM3Z IHC
HPA018221 Anti-DUSP26 IHC,WB
HPA006465 Anti-ECD IHC,WB,ICC-IF
HPA049331 Anti-EFHD1 IHC,WB,ICC-IF
HPA007397 Anti-EPHA6 IHC
HPA030879 Anti-FAM101B IHC
HPA009410 Anti-FAM189A1 IHC
HPA008707 Anti-FKBP7 IHC,WB*,ICC-IF
HPA004937 Anti-FMN2 IHC
HPA052324 Anti-G6PC IHC
HPA044371 Anti-GABRD IHC,WB
HPA027463 Anti-GAK IHC,ICC-IF
HPA011343 Anti-GCM1 IHC
HPA039916 Anti-GLB1L3 IHC
HPA002318 Anti-GLDC IHC,WB*
HPA039501 Anti-GLYATL1 IHC,WB
HPA007990 Anti-GTF3A IHC,ICC-IF
HPA007611 Anti-HIPK2 IHC,ICC-IF
HPA036913 Anti-HMGCS1 IHC,WB,ICC-IF
HPA027423 Anti-HMGCS2 IHC,WB
HPA027442 Anti-HMGCS2 IHC,WB
HPA004337 Anti-IFITM3 IHC,WB
HPA054669 Anti-IRX2 IHC,WB
HPA007931 Anti-ISYNA1 IHC
HPA008232 Anti-ISYNA1 IHC,WB
HPA008572 Anti-ITGA3 IHC
HPA005676 Anti-ITGBL1 IHC,WB
HPA000506 Anti-ITIH6 IHC
HPA051637 Anti-KLHL2 IHC
HPA023074 Anti-KLHL26 IHC,WB
HPA049550 Anti-KRT31 IHC
HPA040330 Anti-KRT32 IHC
HPA042482 Anti-KRTAP9-3 IHC
HPA012072 Anti-LASP11 IHC,WB*,ICC-IF
HPA008556 Anti-LGR6 IHC
HPA036706 Anti-LRRIQ4 IHC
HPA002820 Anti-MAGEB1 IHC
HPA039454 Anti-MANSC4 IHC,WB
HPA059457 Anti-MROH2B IHC
HPA017642 Anti-MRS2 IHC,WB
HPA005914 Anti-MSTO1 IHC
HPA049831 Anti-MTMR2 IHC
HPA005466 Anti-MYBBP1A IHC,WB,ICC-IF
HPA024338 Anti-NAPEPLD IHC,WB,ICC-IF
HPA028136 Anti-NASP IHC,WB,ICC-IF
HPA006111 Anti-NFIA IHC,WB*,ICC-IF
HPA006873 Anti-NKAIN1 IHC
HPA007489 Anti-NPSR12 IHC,ICC-IF
HPA048760 Anti-OR2Z1 IHC
HPA015808 Anti-OR9K2 IHC
HPA024524 Anti-OTOP2 IHC
HPA048975 Anti-PDE4C IHC,WB
HPA051038 Anti-PEG10 IHC,ICC-IF
HPA003994 Anti-PHLDA2 IHC
HPA020200 Anti-PHLPP1 IHC
HPA012312 Anti-PHTF2 IHC
HPA045390 Anti-PKN3 IHC
HPA044690 Anti-PNMA5 IHC,ICC-IF
HPA051607 Anti-PPP1R35 IHC
HPA023923 Anti-PPR11 IHC,WB,ICC-IF
HPA048536 Anti-PVALB IHC
HPA019717 Anti-RAB313 IHC,WB*
HPA047820 Anti-RAC3 IHC,WB
HPA008752 Anti-RAD18 IHC,WB
HPA058061 Anti-REEP1 IHC
HPA005681 Anti-RIOK2 IHC,ICC-IF
HPA015733 Anti-RNF152 IHC,WB
HPA005985 Anti-RPS13 IHC
HPA006462 Anti-S100A1 IHC,WB,ICC-IF
HPA019592 Anti-S100A13 IHC,WB*
HPA027613 Anti-S100A14 IHC,ICC-IF
HPA006997 Anti-S100A7 IHC,ICC-IF
HPA013321 Anti-SGK196 IHC,WB,ICC-IF
HPA051248 Anti-SH3BGRL IHC,WB
HPA037690 Anti-SHROOM1 IHC
HPA005911 Anti-SLC16A7 IHC,WB
HPA042377 Anti-SLC39A6 IHC,WB
HPA023748 Anti-SPAG1 IHC,ICC-IF
HPA018038 Anti-SQLE IHC,WB
HPA011173 Anti-SRPRB IHC,WB
HPA039789 Anti-SSSCA1 IHC,WB*,ICC-IF
HPA049106 Anti-STAG3 IHC,WB,ICC-IF
HPA042583 Anti-STARD6 IHC,IF
HPA001467 Anti-STX74 IHC,WB*,ICC-IF
HPA005781 Anti-TACC3 IHC,WB
HPA007066 Anti-TAPBP IHC
HPA000262 Anti-TBC1D9 IHC,ICC-IF
HPA046156 Anti-TCTE3 IHC
HPA017019 Anti-TGFBI IHC
HPA051855 Anti-TMEM110-MUSTN1 IHC
HPA016579 Anti-TMEM222 IHC,ICC-IF
HPA046658 Anti-TMEM47 IHC
HPA018216 Anti-TMEM68 IHC,ICC-IF
HPA005487 Anti-TPX2 IHC,WB,ICC-IF
HPA003054 Anti-TTLL12 IHC,WB
HPA023605 Anti-UBE20 IHC,WB*
HPA042302 Anti-WFDC2 IHC
HPA050514 Anti-WNT3A IHC
HPA006811 Anti-ZBTB7B IHC,WB*,ICC-IF
HPA009637 Anti-ZKSCAN3 IHC,ICC-IF
HPA007023 Anti-ZNF131 IHC
HPA049770 Anti-ZNF627 IHC,WB
HPA039116 Anti-ZNF662 IHC,WB

* 在人和啮齿动物样本中进行WB

  1. Ngan E et al. A complex containing LPP and α-Actinin mediates TGF β-induced migration and invasion of ErbB2-expressing breast cancer cells. J Cell Sci 2013 May 1; 126(0 9):1981–1991. Epub 2013/02/27.
  2. Camilleri M et al. Neuropeptide S receptor induces neuropeptide expression and associates with intermediate phenotypes of functional gastrointestinal disorders. Gastroenterology 2010 Jan;138(1):98–107.e4.
  3. Bozóky B et al. Novel signatures of cancer-associated fibroblasts. Int J Cancer 2013 Jan 15.
  4. Strömberg S et al. Selective expression of Syntaxin-7 protein in benign melanocytes and malignant melanoma. J Proteome Res 2009 Apr;8(4):1639–46.

寻找癌症生物标志物

乳腺癌

乳腺癌作为第二常见的癌症,是迄今为止女性中最常见的癌症。乳腺癌的发病率正稳步上升,但死亡率并没有相应增加。如果能在早期被检测到,对于生活在发达国家的患者预后相对较好,一般五年生存率约为85%。

 

乳腺癌及治疗

虽然癌症通常被称为单一疾病,但它确实是一种多维度疾病。多年来,这种理解已经在发生变化,但许多患者并未接受针对其疾病的最佳治疗。对于癌症患者接受更个性化的治疗,仍然需要新的和更好的方法来对患者进行分层。经典的预后因素如肿瘤分期和分级并不足以对患者的预后进行正确的预估。来自癌症生物标志物的其他信息有望对这种预估作出极大的改善,并最终导致更为个性化的治疗,从而避免对患者进行治疗不足和过度治疗。

乳腺癌患者的主要治疗方法是手术,并通常与辅助治疗相结合。然而,辅助治疗与实质性成本相关并有时会伴有严重的副作用,而且医生已经将过度治疗的减少确定为当今乳腺癌治疗中的主要临床需要。因此,将患者分层为不同的预后类别是非常重要的,因为它可以帮助医生为给定患者选择最为合适的治疗方案。

大多数乳腺癌是激素受体反应性的,即表达雌激素受体(ER)或孕酮受体(PR)。带有这些受体表达的肿瘤患者可以接受辅助内分泌治疗,例如他莫昔芬

乳腺癌也可表达HER2蛋白(人表皮生长因子受体2),表达该蛋白的肿瘤患者可接受曲妥珠单抗的辅助治疗。

辅助治疗也可以包括化学疗法或放射疗法。

 

RBM3

RNA结合基序蛋白3(RBM3)是一种RNA和DNA结合蛋白,其功能尚未完全阐明。该蛋白质已被证明在亚低温中可作为一种早期事件而实现表达,并也在与细胞应激相关的其他条件下发生表达,例如葡萄糖剥夺和缺氧。在应激条件下,RBM3被认为可通过帮助维持生存所需的蛋白合成来对细胞实现保护。近期研究还显示RBM3可减弱前列腺癌细胞中的干细胞样特性。

通过人类蛋白质图谱(HPA),RBM3作为一种潜在的肿瘤学生物标志物可通过作为HPA项目(proteinatlas.org)的一部分在被调查的几种癌症中因为存在差异表达模式而得以鉴定

使用抗RBM3抗体HPA003624的IHC分析显示其在正常乳腺组织中的弱表达模式,但在乳腺癌组织中则呈分层模式(图1)。研究人员还进一步研究了其在较大乳腺癌队列中的表达,以及RBM3的表达显示出与延长的生存率相关

 

  1. Ehlén Å (2011) PhD Thesis: The role of RNA-binding motif 3 in epithelial ovarian cancer: A biomarker discovery approach.
  2. Zeng Y et al. (2013) Stress response protein RBM3 attenuates the stem-like properties of prostate cancer cells by interfering with CD44 variant splicing. Cancer Res. May 10. [Epub ahead of print].
  3. Berglund L et al. (2008) A gene-centric human protein atlas for expression profiles based on antibodies. Molecular & Cellular Proteomics 7:2019–2027.
  4. Uhlén M et al. (2010) Towards a knowledge-based Human Protein Atlas. Nat Biotechnol 28(12):1248–50.
  5. Jögi A et al. (2009) Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer. Mod Pathol. Dec;22(12):1564–74.

Figure 1. Immunohistochemical analysis using the Anti-RBM3 antibody (HPA003624) shows weak expression in normal breast tissue (A) and differential expression, varying from weak to strong in tumor breast samples (B, C).

图1. 使用抗RBM3抗体(HPA003624)的免疫组化分析显示在正常乳腺组织中的弱表达(A)和差异表达,在肿瘤乳腺样品(B,C)中从弱到强的变化

 

RBM3作为乳腺癌的预后标志物

在确定RBM3可作为潜在的预后生物标志物后,研究人员进一步研究了较大乳腺癌队列中RBM3蛋白的表达。在一组500名患有II期浸润性乳腺癌的绝经前女性患者中发现RBM3的表达与小低级别的雌激素受体(ER)阳性肿瘤相关。在分析ER阳性患者的亚组时,RBM3可作为无复发生存(RFS)的独立预测因子。 如图2所示,与表达低水平RBM3的肿瘤患者相比,表达高水平RBM3蛋白的肿瘤患者的生存率有所提高。

在来自各种形式癌症的许多不同患者群组中对RBM3蛋白表达进行了进一步的分析。发现RBM3表达水平与乳腺、结肠、卵巢、睾丸、尿路上皮和前列腺癌以及恶性黑素瘤患者的生存率存在显着关联。

总结来说,RBM3在乳腺癌以及其他多种癌症中可作为优秀的预后标志物

 

图2. 根据ER阳性乳腺癌患者中RBM3的表达而进行的无复发生存(RFS)Kaplan-Meier(生存期)分析。 根据高和低的RBM3表达将患者分成两组

 

RBM3 抗体

Atlas Antibodies的产品目录中有两种抗RBM3抗体; Triple A多克隆抗体HPA003624和PrecisA单克隆抗体 AMAb90655。单克隆抗RBM3抗体 AMAb90655在人内细胞系的Western Bot分析中显示出优异的特异性,并可常规用于在IHC中对福尔马林固定的石蜡包埋组织进行染色(图3)。

 

图3. 使用 AMAb90655对乳腺癌(左)和前列腺癌(右)中RBM3表达的免疫组化分析显示肿瘤细胞中的核阳性。WB图像显示使用 AMAb90655在人内细胞系RT4裂解物中与预期相符的17kDa条带

 

  1. Jögi A et al. (2009) Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer. Mod Pathol. Dec;22(12):1564–74.
  2. Hjelm B et al. (2011) High nuclear RBM3 expression is associated with an improved prognosis in colorectal cancer. Proteomics Clin Appl. Dec;5(11–12):624–35.
  3. Ehlén Å et al (2010) Expression of the RNA-binding protein RBM3 is associated with a favourable prognosis and cisplatin sensitivity in epithelial ovarian cancer. J Transl Med. Aug 20; 8:78.
  4. Ehlén Å et al. (2011) RBM3-regulated genes promote DNA integrity and affect clinical outcome in epithelial ovarian cancer. Transl Oncol. Aug;4(4):212–21.
  5. Boman K et al. (2013) Decreased expression of RNA-binding motif protein 3 correlates with tumour progression and poor prognosis in urothelial bladder cancer. BMC Urol. 2013;13:17.
  6. Jonsson L et al. (2011) High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression. Diagn Pathol. Sep 28;6:91.
  7. Jonsson L et al. (2011) Low RBM3 protein expression correlates with tumour progression and poor prognosis in malignant melanoma: an analysis of 215 cases from the Malmö Diet and Cancer Study. J Transl Med. Jul 21;9:114.

颗粒蛋白

颗粒蛋白是一种从单一前体蛋白质切割下来的分泌糖基化肽家族。信号肽的切割可产生成熟的颗粒蛋白,其可以进一步切割成多种活性肽。这些裂解产物被命名为颗粒蛋白A、颗粒蛋白B、颗粒蛋白C等。肽和完整的颗粒蛋白均可调节细胞的生长。颗粒蛋白家族的不同成员可作为抑制剂、刺激剂或对细胞生长具有双重作用。颗粒蛋白家族成员在正常发育、伤口愈合和肿瘤发生中是重要的[由RefSeq提供, Jul 2008]。

在Elkabets等人的论文中,通过研究将GRN表达的骨髓细胞招募到小鼠中的反应性肿瘤中来研究GRN表达在反应性肿瘤发作中的作用。某些肿瘤可以促进位于远端解剖部位的其他肿瘤或转移细胞的生长,这被称为肿瘤诱发。在这项研究中,经严格培养的人类乳腺癌细胞被植入到小鼠体内,并显示这些细胞刺激了其他致瘤性较低的惰性转化细胞的生长。GRN被鉴定为诱发骨髓细胞中最为上调的基因。表达GRN的细胞诱导驻留的成纤维细胞表达促进恶性肿瘤进展的基因。 也存在关于抗癌疗法是否可能涉及靶向GRN或活化的GRN表达细胞,从而破坏促进癌症进展的这些通信细胞系的推测。

通过使用抗GRN抗体HPA028747分析来自一组乳腺癌患者的肿瘤组织,显示高GRN表达与最具攻击性的三阴性、基底样肿瘤亚型相关并可降低患者生存率(图4)

 

  1. Elkabets M et al. Human tumors instigate granulin-expressing hematopoietic cells that promote malignancy by activating stromal fibroblasts in mice. J Clin Invest 2011 Feb 1;121(2):784–99.

图4. 使用抗体 HPA028747表明GRN的表达与侵袭性肿瘤亚型相关并可降低乳腺癌患者的存活率。左图显示了每种类别(三阴性[TN] /基底或非基底)具有高GRN阳性率,而右侧的Kaplan-Meier分析则显示GRN阳性(绿色)或GRN阴性(蓝色)表达和生存期之间的相关性。

 

颗粒蛋白抗体

在Atlas Antibodies的产品目录中,有两种多克隆抗GRN抗体; HPA008763HPA028747

 

使用抗GRN抗体(HPA008763)对人胰腺组织进行IHC染色,在外分泌腺细胞中显示出强烈的胞浆阳性。ICC-IF显示A-431细胞中囊泡的阳性。

 

使用抗GRN抗体HPA028747的IHC分析显示在正十二指肠组织中腺体细胞的强胞浆阳性和U-251MG细胞中的囊泡阳性。

 

Anillin

Anillin作为微丝的亚基是一种肌动蛋白结合蛋白,而微丝是细胞骨架成分之一。Anillin在大多数细胞中表达并参与基本的细胞功能,例如运动、分裂和信号转导。 对anillin表达的研究表明它在多种人类肿瘤中过表达。

 

Anillin在乳腺癌中作为治疗预测性预后生物标志物

使用抗ANLN抗体HPA005680对由467例来自被诊断患有乳腺癌患者样品组成的患者队列进行Anillin表达分析。与表达低水平anillin的肿瘤患者相比,表达高水平anillin的肿瘤患者的无复发生存率(RFS)降低(图5A)。在分析乳腺癌特异性生存期时,可以看到anillin的表达与降低的生存率之间具有相同关联性(BCSS,图5B)。在O'Leary等人的一项研究中,通过Cox回归分析证实了anillin对预后的影响。在单变量和多变量分析中,高anillin表达与BCSS和RFS降低相关,并会根据肿瘤大小和等级、诊断年龄、淋巴结、ER-、PR-、HER2-和Ki67状态发生调整。

总结来说,anillin在乳腺癌中是一种较差的预后标志物

 

图5.根据乳腺癌患者的aniliin表达,无复发(A)和乳腺癌特异性存活(B)的Kaplan-Meier(生存)分析。根据高和低的aillin表达将患者分成两组。

 

  1. O´Leary PC et al. Systematic antibody generation and validation via tissue microarray technology leading to identification of a novel protein prognostic panel in breast cancer. BMC Cancer. 2013 Apr 2;13:175.

 

Anillin 抗体

Atlas Antibodies产品目录中有三种抗ANLN抗体; PrecisA单克隆抗体AMAb90660和AMAb90662以及Triple A多克隆抗体 HPA005680

 

抗ANLN抗体(HPA005680)通过IHC在人睾丸生精管细胞中显示出强的核阳性。在ICC-IF中,A-431细胞的细胞核(但不是核仁)染色阳性,而在WB中抗体在RT-4和U-251 MG的细胞裂解物中检测到符合预测大小的条带。

抗ANLN抗体 AMAb90660在肺腺癌的一部分肿瘤细胞中显示出强的核免疫反应性,并且在人类细胞系U-251MG中具有符合预测大小的条带

AMAb90662 抗ANLN抗体在结直肠癌的一部分肿瘤细胞中显示出强的核免疫反应性,并且在人U-251 MG细胞中显示出符合预测大小的条带。