The p53‐mediated sensitivity of cancer cells to chemotherapeutic agents is conditioned by the status of the retinoblastoma protein

• DOI: 10.1002/path.2612
• Publication Date: 2009-08-11T17:00:23Z
• Authors: Massimo Derenzini; Elisa Brighenti; Giulio Donati; Manuela Vici; Claudio Ceccarelli; Donatella Santini; Mario Taffurelli; Lorenzo Montanaro; Davide Treré
• Keywords: Retinoblastoma; Retinoblastoma protein

Abstract Despite the well‐established function of p53 in determining cell cycle arrest and/or apoptosis response to cytostatic/cytotoxic stresses, role status chemotherapeutic agents human cancers has been not clearly defined. We wondered whether this was due fact that p53‐mediated chemotherapy drugs might be conditioned by retinoblastoma protein (pRb), a downstream factor pathway activated stabilization, which is frequently disrupted cancer. The dependence chemosensitivity on pRb first investigated prospective study prognostic relevance breast cancer patients treated with adjuvant (5‐fluorouracil, methotrexate and cyclophosphamide). Univariate analysis disease‐free survival (DFS) indicated status, immunohistochemically evaluated, had no predictive value if considered independently status. However, neither lost nor hyperphosphorylated, significantly associated prognosis and, multivariate DFS including established clinical histopathological parameters, found only predicting progression disease. then studied 5‐fluorouracil or doxorubicin treatment three lines. these cells strictly dependent either RB1 silencing hyperphosphorylation, caused p16(INK4a) silencing, strongly reduced agents. These results demonstrated that: (a) induces effect unaltered pathway; (b) can actually predict outcome group patients. Copyright © 2009 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.