Merck
  • Home
  • Search Results
  • AMP-activated kinase (AMPK) regulates activity of HER2 and EGFR in breast cancer.

AMP-activated kinase (AMPK) regulates activity of HER2 and EGFR in breast cancer.

Oncotarget (2015-07-06)
Teraneh Z Jhaveri, Juhyung Woo, Xiaobin Shang, Ben Ho Park, Edward Gabrielson
ABSTRACT

AMP-activated Protein Kinase (AMPK) activity retards growth of many types of cancers. Investigating effects of AMPK activation on breast cancer cell signaling and survival, we found that breast cancer cell lines with amplification and over-expression of HER2 or EGFR are 2- to 5-fold more sensitive to cytotoxic effects of AICAR, a canonical pharmacological activator of AMPK, than breast cancer cell lines lacking HER2 or EGFR overexpression. Paralleling effects on cell survival, AICAR leads to dose- and time-dependent inhibition of HER2 and EGFR in HER2-amplified breast cancer cells, with activation of AMPK and suppression of HER2/ EGFR activity preceding commitment to cell death. Transfection of constitutively active AMPKα also leads to decreased HER2 and EGFR phosphorylation, reduced downstream signaling associated with these receptor tyrosine kinases (RTKs), and reduced breast cancer cell growth, confirming effects of AMPK activity on HER2/ EGFR. Ensuing co-immunoprecipitation experiments demonstrated an interaction of HER2 with AMPK and an in vitro phosphorylation assay found that HER2 and EGFR contain sequences that are potential substrates for AMPK. Our results lead us to postulate that AMPK regulates HER2 and EGFR activity in HER2-amplified breast cancer cells and thus activation of AMPK might provide therapeutic benefit in such cancers.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
チアゾリルブルーテトラゾリウムブロミド, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥97.5% (HPLC)
Sigma-Aldrich
チアゾリルブルーテトラゾリウムブロミド, 98%
Sigma-Aldrich
ヨウ化プロピジウム, ≥94.0% (HPLC)
Sigma-Aldrich
ヒドロコルチゾン, BioReagent, suitable for cell culture
Sigma-Aldrich
エタノール, JIS special grade, ≥99.5%
Sigma-Aldrich
エチルアルコール(純粋), 190 proof, ACS spectrophotometric grade, 95.0%
Sigma-Aldrich
ヨウ化プロピジウム 溶液, solution (1.0 mg/ml in water)
Sigma-Aldrich
ヒドロコルチゾン, ≥98% (HPLC)
Sigma-Aldrich
エタノール, SAJ first grade, ≥99.5%
Sigma-Aldrich
ヒドロコルチゾン, γ-irradiated, powder, BioXtra, suitable for cell culture
Sigma-Aldrich
AICAR, ≥98% (HPLC), powder
Sigma-Aldrich
ビシンコニン酸 二ナトリウム塩 水和物, ≥98% (HPLC)
Sigma-Aldrich
エタノール, ≥99.5%, suitable for HPLC
Supelco
エタノール標準品10% (v/v), 10 % (v/v) in H2O, analytical standard
Sigma-Aldrich
ヒドロコルチゾン, meets USP testing specifications
Sigma-Aldrich
エタノール, JIS special grade, 94.8-95.8%
Sigma-Aldrich
エタノール, ≥99.5%
Sigma-Aldrich
5-アミノ-4-イミダゾールカルボキサミド, 95%
Sigma-Aldrich
エタノール, JIS first grade, 94.8-95.8%
Sigma-Aldrich
Ethanol Fixative 80% v/v, suitable for fixing solution (blood films)
Sigma-Aldrich
エタノール, ≥99.5%, SAJ super special grade
Sigma-Aldrich
エタノール, JIS 300, ≥99.5%, for residue analysis
Sigma-Aldrich
エタノール, ≥99.5%, suitable for fluorescence
Sigma-Aldrich
エタノール, JIS 1000, ≥99.5%, for residue analysis
Sigma-Aldrich
エタノール, ≥99.5%, suitable for absorption spectrum analysis
Sigma-Aldrich
MISSION® esiRNA, targeting human PRKAA2
Sigma-Aldrich
MISSION® esiRNA, targeting mouse Prkaa2