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p21WAF1/CIP1 gene is inactivated in metastatic prostatic cancer cell lines by promoter methylation

S R J Bott1, M Arya, R S Kirby

  • 1Prostate Cancer Research Centre, Institute of Urology, University College London, London, UK. simonrjbott@doctors.org.uk

Prostate Cancer and Prostatic Diseases
|November 9, 2005
PubMed
Abstract

Insights

Methylation silences the p21WAF1/CIP1 tumor suppressor gene in metastatic prostate cancer. Demethylation reactivates its expression, suggesting a therapeutic target for prostate cancer treatment.

Area of Science:

  • Molecular Biology
  • Cancer Genetics
  • Epigenetics

Background:

  • p21WAF1/CIP1 functions as a tumor suppressor gene (TSG).
  • Loss of p21WAF1/CIP1 gene expression is observed in various solid tumors.
  • Investigating p21WAF1/CIP1 in metastatic prostate cancer is crucial.

Purpose of the Study:

  • To determine p21WAF1/CIP1 expression in metastatic prostate cancer cell lines.
  • To investigate the methylation status of the p21WAF1/CIP1 promoter in these cell lines.

Main Methods:

  • Utilized PC3, LNCaP, and DU145 metastatic prostate cancer cell lines.
  • Treated cell lines with the demethylating agent 5-Aza-2 deoxycytidine (5-Aza-CdR).
  • Analyzed p21WAF1/CIP1 mRNA expression via RT-PCR and promoter sequencing.

Main Results:

  • p21WAF1/CIP1 expression was low/undetectable in metastatic prostate cancer cells but reactivated by 5-Aza-CdR.
  • Promoter sequencing revealed methylation at the 5' end of a CpG island in metastatic cell lines.
  • Key binding sites, including the Sis-inducible element (SEI)-1-a STAT1-binding site, were methylated.

Conclusions:

  • Demethylation enhances p21WAF1/CIP1 expression in metastatic prostate cancer cell lines.
  • Methylation of promoter cytosine residues, including critical binding sites, is evident.
  • Promoter methylation may inactivate the p21WAF1/CIP1 TSG by inhibiting STAT1 signaling in prostate cancer.

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