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The Interplay of AMP‐Activated Protein Kinase and Androgen Receptor in Prostate Cancer Cells
Author(s) -
Shen Min,
Zhang Zhen,
Ratnam Manohar,
Dou Q. Ping
Publication year - 2014
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24494
Subject(s) - ampk , androgen receptor , prostate cancer , downregulation and upregulation , protein kinase a , cancer research , amp activated protein kinase , signal transduction , cancer cell , chemistry , endocrinology , microbiology and biotechnology , medicine , kinase , cancer , biology , biochemistry , gene
AMP‐activated protein kinase (AMPK) has recently emerged as a potential target for cancer therapy due to the observation that activation of AMPK inhibits tumor cell growth. It is well‐known that androgen receptor (AR) signaling is a major driver for the development and progression of prostate cancer and that downregulation of AR is a critical step in the induction of apoptosis in prostate cancer cells. However, little is known about the potential interaction between AMPK and AR signaling pathways. In the current study, we showed that activation of AMPK by metformin caused decrease of AR protein level through suppression of AR mRNA expression and promotion of AR protein degradation, demonstrating that AMPK activation is upstream of AR downregulation. We also showed that inhibition of AR function by an anti‐androgen or its siRNA enhanced AMPK activation and growth inhibition whereas overexpression of AR delayed AMPK activation and increased prostate cancer cellular resistance to metformin treatment, suggesting that AR suppresses AMPK signaling‐mediated growth inhibition in a feedback mechanism. Our findings thus reveal a novel AMPK‐AR regulatory loop in prostate cancer cells and should have a potential clinical significance. J. Cell. Physiol. 229: 688–695, 2014. © 2013 Wiley Periodicals, Inc.