Epigenetic down regulation of RASSF10 and its possible clinical implication in prostate carcinoma

Temuujin Dansranjavin1, Florian Wagenlehner, Stefan Gattenloehner

  • 1Department of Urology, Pediatric Urology and Andrology, Justus Liebig University Giessen, Giessen, Germany.

The Prostate
|March 15, 2012
PubMed
Abstract

Insights

Ras association domain family 10 (RASSF10) is frequently epigenetically inactivated in prostate cancer (PCa). This tumor suppressor gene

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Ras association domain family (RASSF) genes are tumor suppressors often epigenetically silenced in cancers.
  • RASSF10 is a recently identified member of the RASSF family.
  • The role of RASSF10 in prostate carcinogenesis requires investigation.

Purpose of the Study:

  • To analyze the relevance of RASSF10 in prostate cancer (PCa).
  • To investigate the epigenetic inactivation of RASSF10 in PCa.
  • To explore the functional role of RASSF10 in PCa.

Main Methods:

  • Investigated RASSF10 promoter methylation and mRNA expression in PCa cell lines and primary tissues using bisulfite-pyrosequencing and qRT-PCR.
  • Utilized in situ hybridization for RASSF10 localization.
  • Treated PCa cell lines with demethylating agents (5-aza-2-deoxycytidine and trichostatin A).
  • Assessed RASSF10 function via colony formation and apoptosis assays.

Main Results:

  • RASSF10 mRNA was localized to basal layer cells of the prostate gland.
  • RASSF10 expression loss/reduction in PCa cell lines and tissues correlated with promoter methylation.
  • RASSF10 inactivation was more frequent in PCa than benign prostatic hyperplasia (BPH) tissues.
  • RASSF10 methylation associated with advanced tumor stage and age.
  • RASSF10 inhibited colony formation and promoted apoptosis in functional assays.

Conclusions:

  • Demonstrates frequent epigenetic inactivation of RASSF10 in prostate cancer.
  • Highlights the implication of RASSF10 inactivation in clinical PCa symptoms.
  • Establishes RASSF10 as a potential tumor suppressor in PCa.

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