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Frequent Loss of pRb2/p130 in Human Ovarian Carcinoma

Sbarro Institute for Cancer Research and Molecular Medicine, ¹ Department of Biology, College of Science and Technology, Temple University, ² Department of Microbiology and Immunology, Fels Institute for Cancer Research, Temple University School of Medicine; ³ Department of Pathology and Laboratory Medicine, Drexel University; ⁴ Department of Obstetrics and Gynecology, Thomas Jefferson University, Philadelphia, Pennsylvania; ⁵ Department of Human Pathology and Oncology, University of Siena, Siena; ⁶ Department of Pathology, Catholic University of the Sacred Heart, Rome; ⁷ Centro de Ricerca e Formazione ad Alta Tecnologia delle Scienze Biomediche, Catholic University of the Sacred Heart, Contrada Tappino, Campobasso, Italy

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 G₁-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.

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