Stromal anti-apoptotic androgen receptor target gene c-FLIP in prostate cancer

Huihui Ye1, Yirong Li, Jonathan Melamed

  • 1Department of Pathology and Urology, New York University School of Medicine, New York Harbor Healthcare System, New York, New York 10010, USA.

The Journal of Urology
|December 20, 2008
PubMed
Abstract

Insights

Stromal c-FLIP (cellular FLICE-inhibitory protein) is elevated in early prostate cancer, promoting tumor growth and invasion. Its role diminishes as cancer becomes androgen-independent.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The tumor microenvironment critically impacts prostate cancer progression.
  • Androgen receptor signaling regulates prostate cancer cell proliferation via target genes.
  • Cellular FLICE-inhibitory protein (c-FLIP) is an androgen receptor target gene inhibiting apoptosis and promoting androgen independence.

Purpose of the Study:

  • To investigate the role of c-FLIP expression in prostate cancer stromal cells.
  • To determine the association between stromal c-FLIP and prostate cancer development and progression.

Main Methods:

  • Immunohistochemical analysis of c-FLIP expression in 53 androgen-dependent and 21 androgen-independent prostate cancer stromal cells.
  • In vitro coculture systems to assess the impact of stromal c-FLIP overexpression on prostate cancer cell growth and invasion (LNCaP and PC3 cells).

Main Results:

  • Stromal c-FLIP levels were increased in androgen-dependent prostate cancer tissue and correlated with tumor differentiation.
  • Stromal c-FLIP expression was not elevated in androgen-independent prostate cancer.
  • Overexpression of c-FLIP in stromal cells enhanced the in vitro growth and invasion of prostate cancer cells.

Conclusions:

  • Stromal c-FLIP is overexpressed in early-stage prostate cancer.
  • Stromal c-FLIP promotes prostate cancer cell growth and invasion.
  • The role of stromal c-FLIP may be more significant in androgen-dependent disease.

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