Frequent loss of pRb2/p130 in human ovarian carcinoma

Clin Cancer Res. 2004 May 1;10(9):3098-103. doi: 10.1158/1078-0432.ccr-03-0524.

Abstract

Purpose: RB2/p130, a member of the retinoblastoma gene family, maps to human chromosome 16q12.2, a region in which deletions have been found in several human neoplasms including breast, prostatic, and ovarian carcinoma. We sought to evaluate pRb2/p130 protein expression and function in ovarian carcinoma.

Experimental design: pRb2/p130 expression was detected by immunohistochemical and Western blot analyses in 45 primary ovarian carcinoma samples.

Results: Immunohistochemical analysis revealed loss or decrease of pRb2/p130 expression in 18 cases (40%). pRb2/p130 expression was mostly nuclear and inversely correlated to the tumor grade (P < 0.05). Western blot analysis correlated with immunohistochemical expression. Reverse transcription-PCR followed by Southern blot analysis was performed on a representative set of 20 ovarian carcinomas. RB2/p130 mRNA levels were consistent with protein expression. We found a significant increase in the percentage of G(1)-phase-arrested cells in CAOV3 and A2780 ovarian carcinoma cell lines after transduction with an adenovirus carrying the RB2/p130 gene (Ad-CMV-RB2/p130).

Conclusions: These data indicate that loss or decrease of pRb2/p130 expression is a frequent event in ovarian carcinoma and is regulated mostly at the transcriptional level. Moreover, pRb2/p130 overexpression is able to arrest cell growth in ovarian carcinoma cells, suggesting the putative role of pRb2/p130 as a tumor suppressor in this malignancy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Blotting, Western
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Division / genetics
  • Cell Division / physiology
  • Cell Line, Tumor
  • CpG Islands / genetics
  • DNA Methylation
  • DNA Mutational Analysis
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Vectors / genetics
  • Humans
  • Immunohistochemistry
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / physiology
  • Retinoblastoma-Like Protein p130
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

Substances

  • Proteins
  • RBL2 protein, human
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Retinoblastoma-Like Protein p130