Regulation of phosphatase homologue of tensin protein expression by bone morphogenetic proteins in prostate epithelial cells

Travis Jerde, Zhong Wu, Dan Theodorescu, Wade Bushman

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)791-800
Number of pages10
JournalProstate
Volume71
Issue number8
DOIs
StatePublished - Jun 1 2011

Fingerprint

Bone Morphogenetic Proteins
Phosphoric Monoester Hydrolases
Prostate
Epithelial Cells
Bone Morphogenetic Protein 4
Proteins
Growth
Tensins
Protein Stability
Prostatic Neoplasms
Phosphoprotein Phosphatases

Keywords

  • Bone-morphogenetic protein
  • Epithelium
  • Phosphatase homologue of tensin analogue
  • Prostate
  • Protein stability

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

Regulation of phosphatase homologue of tensin protein expression by bone morphogenetic proteins in prostate epithelial cells. / Jerde, Travis; Wu, Zhong; Theodorescu, Dan; Bushman, Wade.

In: Prostate, Vol. 71, No. 8, 01.06.2011, p. 791-800.

Research output: Contribution to journalArticle

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abstract = "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.",
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N2 - 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.

AB - 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.

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