Protocadherin-PC promotes androgen-independent prostate cancer cell growth

Prostate. 2006 Jul 1;66(10):1100-13. doi: 10.1002/pros.20446.

Abstract

Background: Protocadherin-PC (PCDH-PC) expression is upregulated in apoptosis-resistant sublines of the LNCaP human prostate cancer (CaP) cell line. Here, we assess the role of PCDH-PC in CaP cells and its mRNA expression in human prostate tissues.

Methods: LNCaP cells transfected with PCDH-PC were tested for their ability to grow in vitro and in vivo in androgen-deprived conditions. PCDH-PC mRNA expression was evaluated by semi-quantitative RT-PCR and by in situ hybridization.

Results: PCDH-PC expression induced Wnt signaling in CaP cells and permitted androgen-independent growth of hormone-sensitive CaP cells. Expression of PCDH-PC-homologous transcripts was low and restricted to some epithelial cells in normal tissue and to CaP cells in tumors. However, hormone-resistant CaP cells expressed significantly higher levels of PCDH-PC-related mRNA.

Conclusions: Our findings suggest a novel mechanism for the progression of CaP involving expression of PCDH-PC. This novel protocadherin induces Wnt signaling, promotes malignant behavior and hormone-resistance of CaP cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Androgens / physiology*
  • Animals
  • Apoptosis / physiology
  • Cadherins / analysis
  • Cadherins / genetics
  • Cadherins / physiology*
  • Cell Line, Tumor
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Mice
  • Mice, Nude
  • Neoplasms, Hormone-Dependent / chemistry
  • Neoplasms, Hormone-Dependent / genetics*
  • Neoplasms, Hormone-Dependent / pathology
  • Neoplasms, Hormone-Dependent / physiopathology*
  • Prostate / chemistry
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / physiopathology*
  • Protocadherins
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology
  • TCF Transcription Factors / physiology
  • Wnt Proteins / genetics
  • Wnt Proteins / physiology
  • Xenograft Model Antitumor Assays

Substances

  • Androgens
  • Cadherins
  • PCDH11Y protein, human
  • Protocadherins
  • RNA, Messenger
  • TCF Transcription Factors
  • Wnt Proteins