The RASSF1A tumor suppressor gene is inactivated in prostate tumors and suppresses growth of prostate carcinoma cells

Igor Kuzmin, John W. Gillespie, Alexei Protopopov, Laura Geil, Koen Dreijerink, Youfeng Yang, Cathy D. Vocke, Fuh Mei Duh, Eugene Zabarovsky, John D. Minna, Johng S. Rhim, Michael R. Emmert-Buck, W. Marston Linehan, Michael I. Lerman

Research output: Contribution to journalArticlepeer-review

149 Scopus citations

Abstract

We analyzed expression status of the recently identified tumor suppressor gene RASSF1A in primary prostate carcinomas and in prostate cell lines. We found complete methylation of the RASSF1A promoter in 63% of primary microdissected prostate carcinomas (7 of 11 samples). The remaining 4 samples (37%) were partially methylated, possibly because of contamination with normal cells. No promoter methylation was observed in matching normal prostate tissues. High levels of RASSF1A transcript and no methylation of RASSF1A promoter were found in explanted primary normal prostate epithelial and stromal cells. Complete silencing and methylation of RASSF1A promoter was observed in five widely used prostate carcinoma cell lines, which acquired the ability to grow in culture spontaneously, including LNCaP, P\C-3, ND-1, DU-145, 22Rv1, and one primary prostate carcinoma immortalized by overexpression of the human telomerase catalytic subunit (RC-58T/hTERT). However, no silencing of RASSF1A was found in four other prostate carcinoma cell lines, which were adapted for cell culture after transformation with human papillomaviral DNA. Suppression of cell growth in vitro was demonstrated after the reintroduction of RASSF1A-expressing construct into LNCaP prostate carcinoma cells. Our data implicate the RASSF1A gene in human prostate tumorigenesis.

Original languageEnglish (US)
Pages (from-to)3498-3502
Number of pages5
JournalCancer research
Volume62
Issue number12
StatePublished - Jun 15 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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