title: Determine the effect of p53 on chemosensitivity.
abstract: The p53 tumor suppressor protein plays a central role in mediating the cellular response to a variety of stresses. Activation of p53 signaling will trigger cell cycle arrest or apoptosis in normal cells, depending on such factors as cell type and genetic context. The ability of a cell to circumvent either of these p53-directed outcomes leads to inappropriate proliferation, thereby contributing to the development of cancer. As such, tumors frequently escape the apoptotic pathway in response to cell stress. DNA-damaging agents, however, achieve significant tumor cytotoxicity in spite of this hallmark characteristic. Tumors treated with DNA-damaging drugs often undergo alternate forms of cell death, such as senescence or mitotic catastrophe, in addition to apoptosis that may ultimately lead to regression. Although not a predictor of chemotherapy response in patients per se, p53 status in tumor-derived cells is frequently a determinant of the death pathway promoted by these agents. The cytotoxic effects of DNA-damaging agents can be readily appreciated using such tools as cell cycle analysis, phopsho-H3(Ser10) immunoblotting, and annexin V detection.
authors.affiliation: Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Emir
authors.initials: E
authors.lastname: Senturk
authors.forename: James J
authors.initials: JJ
authors.lastname: Manfredi
mesh_terms: D017304:Annexin A5 / Q000032:analysis / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D004249:DNA Damage / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D006657:Histones / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008938:Mitosis; D011419:Propidium / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D017304:Annexin A5; D006657:Histones; D016159:Tumor Suppressor Protein p53; D011419:Propidium