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Regulation of phosphatase homologue of tensin protein expression by bone morphogenetic proteins in prostate epithelial cells
Author(s) -
Jerde Travis J.,
Wu Zhong,
Theodorescu Dan,
Bushman Wade
Publication year - 2010
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21295
Subject(s) - pten , tensin , cancer research , prostate cancer , bone morphogenetic protein , gene knockdown , cell growth , prostate , bone morphogenetic protein 2 , biology , pi3k/akt/mtor pathway , chemistry , signal transduction , microbiology and biotechnology , medicine , cancer , cell culture , gene , biochemistry , genetics , in vitro
BACKGROUND Phosphatase homologue of tensin (PTEN) is the most commonly mutated gene in prostate cancer. Bone morphogenetic proteins (BMPs) are known to promote differentiation and inhibit proliferation. Previously published reports from other organ systems led us to investigate a mechanistic relationship between PTEN and BMP signaling in prostate epithelial cells. METHODS We analyzed growth rate and PTEN expression in E6, BPH‐1, and C4‐2B prostate epithelial cells treated with BMP‐4. We also treated doxacyclin‐inducible PTEN‐C4‐2B cells with BMP‐4 and doxacyclin to determine the effect of BMP on growth and PTEN expression in conditions of increasing PTEN expression. We determined the dependency of BMP‐mediated growth inhibition via siRNA knockdown of PTEN expression and BMP treatment. We determined PTEN protein stability by determining the effect of BMP‐4 on PTEN protein at time points after treatment with cyclohexamide, a translation inhibitor. RESULTS We found that BMP‐4 induces PTEN in E6 and BPH‐1 cells and reduces proliferation. Knockdown of PTEN attenuated the growth‐inhibiting effects of BMP‐4 in these cells. BMP‐4 had no effect in PTEN‐negative C4‐2B cells, but doxacyclin‐driven PTEN C4‐2B cells responded to BMP‐4 with enhanced PTEN and growth inhibition. BMP‐4 also increased PTEN protein stability. CONCLUSIONS BMP signaling induces PTEN expression and sustains PTEN protein expression resulting in inhibition of prostate epithelial cell growth. These data are the first to identify a mechanistic linkage between BMP signaling and PTEN in the prostate, both of which are independently identified as tumor suppressors and suggest possible coordinate dysregulation in prostate cancer. Prostate 71:791–800, 2011. © 2010 Wiley‐Liss, Inc.