PMEPA1 promotes androgen receptor‐negative prostate cell proliferation through suppressing the Smad3/4–c‐Myc–p21$^{{\rm Cip1}}$ signaling pathway

• DOI: 10.1002/path.2834
• Publication Date: 2010-12-02T15:40:28Z
• Authors: Rong Liu; Zhongmei Zhou; Jian Huang; Ceshi Chen
• Keywords: Cyclin-Dependent Kinase Inhibitor p21; Male; 0303 health sciences; Membrane Proteins; Prostatic Neoplasms; Mice, SCID; 3. Good health; Neoplasm Proteins; Gene Expression Regulation, Neoplastic; Proto-Oncogene Proteins c-myc; Mice; 03 medical and health sciences; Receptors, Androgen; Gene Knockdown Techniques; Animals; Humans; Smad3 Protein; Neoplasm Transplantation; Cell Proliferation; Signal Transduction; Smad4 Protein

Abstract The PMEPA1 gene has been shown to suppress the androgen receptor (AR) and TGFβ signaling pathways is abnormally expressed in prostate tumours. However, role mechanism action of AR‐negative cancer are unclear. Here, we demonstrate that inhibition suppresses RWPE1 PC‐3 cell proliferation through up‐regulating p 21 transcription. Additionally, overexpression p21 expression promotes proliferation. induced by as a negative feedback loop Smad3 phosphorylation nuclear translocation; up‐regulates c‐Myc; down‐regulates p21; functions depend on its Smad2/3 binding motif. Consistently, depletion Smad3/4, but not Smad2, blocks PMEPA1's regulating c‐Myc p21. Importantly, stable inhibits xenograft growth. Finally, found overexpressed subset lines These findings suggest may promote Copyright © 2011 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.