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Clinical Cancer Research Vol. 10, 8085-8093, December 1, 2004
© 2004 American Association for Cancer Research


Experimental Therapeutics, Preclinical Pharmacology

pRb2/p130 Decreases Sensitivity to Apoptosis Induced by Camptothecin and Doxorubicin but not by Taxol

Tiziana Tonini1,2, Chiara Gabellini1,3, Luigi Bagella1,2, Giuseppina D’Andrilli1,4, Valeria Masciullo1, Gaetano Romano5, Giovanni Scambia4, Gabriella Zupi3 and Antonio Giordano1,2

1 Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, Pennsylvania; 2 Department of Human Pathology and Oncology, University of Siena Nuovo Policlinico "Le Scotte," Siena, Italy; 3 Experimental Chemotherapy Laboratory, Experimental Research Center, Regina Elena Cancer Institute, Rome, Italy; 4 Centro di Ricerca e Formazione ad Alta Tecnologia delle Scienze Biomediche, Catholic University of the Sacred Heart, Contrada Tappino, Campobasso, Italy; and 5 Department of Neurosurgery, Thomas Jefferson University, Jefferson Hospital for the Neurosciences, Philadelphia, Pennsylvania

Purpose: In addition to their original function as cell cycle regulators, retinoblastoma (Rb) family members were recently reported to modulate the sensitivity of cancer cells to chemotherapeutic agents. The purpose of this study is to investigate the possible role of pRb2/p130 in the sensitivity of ovarian cancer to camptothecin, doxorubicin, and taxol.

Experimental Design: pRb2/p130 was overexpressed in the CAOV-3 ovarian cancer cell line, and the effect of pRb2/p130 overexpression on sensitivity to apoptosis trigged by IC50 doses of different drugs was evaluated by various methods, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, and Western blot analyses.

Results: The results reported in this study support the conclusion that overexpression of pRb2/p130 in the CAOV-3 ovarian cancer cell line lacking wild-type p53 is able to inhibit apoptosis triggered by camptothecin and doxorubicin through the c-Jun NH2-terminal kinase signaling transduction pathway. Conversely, taxol-induced cell death is not influenced by the pRb2/p130 protein level.

Conclusions: A careful analysis of pRb2/p130 expression in tumor specimens could help to identify the best clinical protocol to be used for each patient, improving efficacy and tolerance and therefore offering additional progress in the treatment of advanced ovarian cancer.




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A. Sharma, C. E.S. Comstock, E. S. Knudsen, K. H. Cao, J. K. Hess-Wilson, L. M. Morey, J. Barrera, and K. E. Knudsen
Retinoblastoma Tumor Suppressor Status Is a Critical Determinant of Therapeutic Response in Prostate Cancer Cells
Cancer Res., July 1, 2007; 67(13): 6192 - 6203.
[Abstract] [Full Text] [PDF]




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Copyright © 2004 by the American Association for Cancer Research.