Overexpression of AMPKgamma 2 enhances tumorigenicity of Ovarian Cancer Cells

Abstract

AMP-activated protein kinase (AMPK) is a highly conserved serine-threonine protein kinase which acts as a sensor monitoring cellular energy status and to maintain energy homeostasis in eukaryotic cells. It is activated under a variety of metabolic stresses such as hypoxia, glucose starvation and heat shock etc. Recent findings have shown that artificially activated AMPK by 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR) can strongly inhibit cell proliferation in tumor cells via cell cycle arrest and/or suppression of biosynthetic processes. However, the response varies in different cancer cell types. In the present study, we characterized the functions of AMPKγ2, one of the AMPK subunits, in human ovarian cancer cells. By quantitative RT-PCR and Western blot analyses, we found that the expression levels of AMPKγ2 were higher in human ovarian cancer samples, but were diminished under hypoxia or glucose deprivation treatments. Transient or stably overexpressed AMPKγ2 remarkably reduced the levels of phospho-AMPK (p-AMPK) and the AMPK downstream target, phospho-acetyl-CoA carboxylase (p-ACC), in human ovarian cancer cells. Intriguingly, enforced expression of AMPKγ2 significantly increased cell proliferation, anchorage-independent growth ability, and resistance to the growth-suppressive effect of AICAR. Altogether, these results suggest that AMPKγ2, acts as a negative regulator of AMPK, retards the responses to AICAR treatments, and enhances tumorigenicity of ovarian cancer.