Frequent Loss of pRb2/p130 in Human Ovarian Carcinoma

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.

Cell Cycle Genes in Ovarian Cancer

“…No alterations of the RB2/p130 gene were found in 43 tumors analyzed by Alvi et al (49). In a recent study on 45 primary ovarian carcinomas, pRb2/p130 protein was lost or decreased in 40% of the specimens, and the enhanced, adenovirus-mediated pRb2/p130 syn-thesis leads to a drastic growth arrest in the G 1 phase of the cell cycle in ovarian cancer cell lines, suggesting its tumor suppressor function in ovarian cancer (50). p21 CIP1/WAF1 .…”

Regulation of cellular senescence by Rb2/p130

“…One would expect that decreased levels of Rb2/p130 observed in strongly proliferating tumor cells simply result from decreased protein stability as is the case in normally cycling cells (Tedesco et al, 2002). However, Rb2/p130 in tumors seemed to be downregulated at the transcriptional level and not by posttranslational modifications (Milde-Langosch et al, 2001;D'Andrilli et al, 2004). Therefore, deregulation of Rb2/p130 expression could well be an important event in development and/or progression of tumors by impairing the onset of the senescence program.…”

pRb2/p130: a new candidate for retinoblastoma tumor formation

“…Inactivation of its biological function owing to genetic or epigenetic mechanisms or to physical interaction with viral oncoproteins has been described in neoplasms of different organs. In particular, an active role for pRb2/p130 has been postulated in the genesis of neoplasms of the lung (Claudio et al, 2000), breast (Macaluso et al, 2003), ovary (D'Andrilli et al, 2004) and non-Hodgkin's lymphomas . In addition, inactivation of its biological function owing to interaction with viral oncoproteins has also been described in mesothelioma (Mutti et al, 1998) and in AIDS-related lymphomas (De Falco et al, 2003).…”