Alterations in the p53 tumor suppressor gene stand out as the most common alteration in many cancers including 96% of ovarian serous carcinoma. The fact that most p53 alterations in tumors are missense mutations suggests that cells expressing mutant p53 have an inherent biologic advantage (often termed gain of function (GOF)) over tumors lacking p53. Mouse models directly examined the role of p53 mutants in tumorigenesis and show an increased invasiveness and aggressive nature of mutant p53 tumors as opposed to those lacking p53. An additional prerequisite for GOF is the stabilization of mutant p53 proteins by various signaling pathways. The emerging themes by which mutant p53 exhibits its gain of function are 1) through formation of mutant p53 complexes with other proteins that modify their activities (p63 and p73, for example), and 2) by interaction of mutant p53 with other transcription factors (SREBP and Ets2, for example) that bring a potent transcriptional activation domain to promoters not normally regulated by wild type p53. An understanding of the mechanisms that drive mutant p53 activities in ovarian serous carcinoma is needed.
Citation Format: Guillermina Lozano. Mutant p53 activities in tumor development. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr IA21.