EMAIL THIS PAGE TO A FRIEND

Cancer science

Epigenetic deregulation of Ellis Van Creveld confers robust Hedgehog signaling in adult T-cell leukemia.


PMID 24996003

Abstract

One of the hallmarks of cancer, global gene expression alteration, is closely associated with the development and malignant characteristics associated with adult T-cell leukemia (ATL) as well as other cancers. Here, we show that aberrant overexpression of the Ellis Van Creveld (EVC) family is responsible for cellular Hedgehog (HH) activation, which provides the pro-survival ability of ATL cells. Using microarray, quantitative RT-PCR and immunohistochemistry we have demonstrated that EVC is significantly upregulated in ATL and human T-cell leukemia virus type I (HTLV-1)-infected cells. Epigenetic marks, including histone H3 acetylation and Lys4 trimethylation, are specifically accumulated at the EVC locus in ATL samples. The HTLV-1 Tax participates in the coordination of EVC expression in an epigenetic fashion. The treatment of shRNA targeting EVC, as well as the transcription factors for HH signaling, diminishes the HH activation and leads to apoptotic death in ATL cell lines. We also showed that a HH signaling inhibitor, GANT61, induces strong apoptosis in the established ATL cell lines and patient-derived primary ATL cells. Therefore, our data indicate that HH activation is involved in the regulation of leukemic cell survival. The epigenetically deregulated EVC appears to play an important role for HH activation. The possible use of EVC as a specific cell marker and a novel drug target for HTLV-1-infected T-cells is implicated by these findings. The HH inhibitors are suggested as drug candidates for ATL therapy. Our findings also suggest chromatin rearrangement associated with active histone markers in ATL.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

06-599
Anti-acetyl-Histone H3 Antibody, 100 µg, Detect acetyl-Histone H3 with Anti-acetyl-Histone H3 Antibody (Rabbit Polyclonal Antibody), that has been shown to work in WB, ICC, ChIP, ChIP-seq.
SAB1405772
Anti-EVC antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA008703
Anti-EVC antibody produced in rabbit, Ab1, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
HPA016046
Anti-EVC antibody produced in rabbit, Ab2, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
I5381 IgG from mouse serum, reagent grade, ≥95% (SDS-PAGE), lyophilized powder
SRP6170
IL-2 human, recombinant, expressed in HEK 293 cells, ≥95% (SDS-PAGE)
SRP3085 IL-2 human, Animal-component free, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), cell culture tested
57600 Interleukin-2 human, ≥98.0% (GE), recombinant, expressed in E. coli, ~10000 U/mL
I2644 Interleukin-2 human, IL-2, recombinant, expressed in E. coli, lyophilized powder, suitable for cell culture
I7908 Interleukin-2 human, recombinant, expressed in Pichia pastoris, suitable for cell culture
H7041 Interleukin-2 human, IL-2, recombinant, expressed in HEK 293 cells, cell culture tested, endotoxin tested
SAB4700062
Monoclonal Anti-CD4-FITC , (N-terminal) antibody produced in mouse, clone MEM-241, purified immunoglobulin, buffered aqueous solution
F1773 Monoclonal Anti-CD4−FITC antibody produced in mouse, clone Q4120, purified immunoglobulin, buffered aqueous solution
SAB1402769
Monoclonal Anti-EVC antibody produced in mouse, clone 3C4, purified immunoglobulin, buffered aqueous solution