NEW YORK (Reuters Health) - Loss of Rb2/p130 is a common event in ovarian carcinoma and its overexpression arrests cell growth in ovarian carcinoma cells, according to a report in the May 1st issue of Clinical Cancer Research.
“The identification of the potential role of Rb2/p130 as a suppressor gene in ovarian carcinomas will increase our knowledge of the alterations responsible for this pathology and possibly give new prognostic indications concerning disease outcome,” Dr. Antonio Giordano from Temple University, Philadelphia, told Reuters Health.
Dr. Giordano and colleagues previously demonstrated that Rb2/p130 acts as a tumor suppressor gene in vivo and in vitro in SKOV3 ovarian carcinoma cells. In this study, they investigated the role of Rb2/p130 in the pathogenesis of ovarian carcinoma using immunohistochemical studies of 45 ovarian carcinoma specimens, 4 cell lines, and 4 nonneoplastic ovarian samples.
Eighteen of 45 primary ovarian adenocarcinomas (40%) showed loss or decrease of Rb2/p130 expression, the authors report, and there was an inverse correlation between nuclear expression of Rb2/p130 and the nuclear grade of the tumor.
In RT-PCR analyses, Rb2/p130 transcript was detectable in all but one of the ovarian samples, the report indicates, but expression was considerably weaker compared with benign ovarian surface epithelium in a significant percentage of the ovarian tumors.
Interestingly, the researchers note, there were no mutations in Rb2/p130 in the ovarian carcinoma cell lines and tumor samples analyzed.
Overexpression of Rb2/p130 in ovarian carcinoma cell lines CAOV3 and A2780 resulted in a significant increase in the number of cells arrested in G1 growth phase, the investigators report.
“All the ovarian carcinoma samples analyzed in this study were [incapable] of properly regulating Rb2/p130 expression, and this lack of expression resulted in the ovarian cells becoming cancerous,” Dr. Giordano said.
“However, upon re-expressing Rb2/p130, we could not only control cell growth but in fact we were able to arrest growth in these cancerous cells. Therefore, Rb2/p130 is potentially a valuable tool for future clinical applications in regulating unchecked cellular proliferation in ovarian carcinomas.”
“Loss of Rb2/p130 expression has been demonstrated in breast, prostate, hepatic, endometrial, and nasopharyngeal carcinoma and non-Hodgkin’s and Burkitt’s lymphoma, as well as small cell and non-small cell lung cancers,” Dr. Giordano added. “We plan to study the therapeutic potential of medically correcting the loss of Rb2/p130 expression in many human cancers.”
Rb2/p130 is a potential ovarian carcinoma prognostic molecular biomarker, Dr. Giordano concludes, and may help clinicians “to more accurately diagnose and evaluate individual patients and to personally tailor their patients’ individual cancer treatments.”
Source: Clin Cancer Res 2004;10:3098-3103. [ Google search on this article ]
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