Stromal Anti-Apoptotic Androgen Receptor Target Gene c-FLIP in Prostate Cancer

Huihui Ye, Yirong Li, Jonathan Melamed, Patrice Pearce, Jianjun Wei, Luis Chiriboga, Zhengxin Wang, Iman Osman, Peng Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Purpose: The tumor microenvironment significantly influences prostate cancer progression. Androgen receptor exerts its effect through downstream target genes to regulate prostate cancer cell proliferation. The c-FLIP gene was recently shown to be an androgen receptor target gene. c-FLIP is an inactive homologue of caspase-8 and, thus, it inhibits the death receptor mediated apoptosis pathway. c-FLIP over expression was shown to accelerate the progression of prostate cancer cells to androgen independence. We evaluated the role of c-FLIP expression in stromal cells in prostate cancer development. Materials and Methods: We examined c-FLIP expression in 53 androgen dependent and 21 androgen independent prostate cancer stromal cells by immunohistochemical analysis. The effects of c-FLIP over expression in stromal cells on the growth and invasion of LNCaP and PC3 prostate cancer cells were determined in indirect coculture systems. Results: At the androgen dependent stage the stromal c-FLIP level was increased in prostate cancer tissue. The expression level of stromal c-FLIP was associated with tumor differentiation. However, stromal c-FLIP expression was not increased in androgen independent human prostate cancer. c-FLIP over expression in stromal cells stimulated the growth and invasion of prostate cancer, including LNCaP and PC3 cells in vitro. Conclusions: These results indicate the over expression of stromal c-FLIP and its function for promoting prostate cancer growth and invasion.

Original languageEnglish (US)
Pages (from-to)872-877
Number of pages6
JournalJournal of Urology
Issue number2
StatePublished - Feb 2009


  • androgen
  • disease progression
  • prostate
  • prostatic neoplasms
  • receptors
  • stomal cells

ASJC Scopus subject areas

  • Urology


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