Role of p53 and Rb in Ovarian Cancer

Abstract

Ovarian cancer remains a major health concern worldwide, primarily in postmenopausal women. Among the most common genetic alterations in human sporadic epithelial ovarian cancer (EOC) are p53 mutations, defective retinoblastoma (RB) pathway (p16 INK4a /RB) and activation of oncogenes such as c-myc, K-ras and Akt. Although these alterations are frequently associated with poor clinical prognosis, their specific contributions to EOC formation remain unclear. In order to gain a better understanding of the roles of these proteins in vivo, a number of mouse models have been generated, largely based upon inducing specific genetic lesions in the ovarian surface epithelium from which the majority of carcinomas are thought to arise in humans. Here, we review the role of tumor suppressor p53 and the Rb pathway in EOC with particular attention to association of p53 to high grade serous carcinomas as opposed to low grade and benign tumors. We also provide an overview of the utility and application of genetically engineered mouse models, in particular towards rational drug design and development of improved imaging techniques in ovarian cancer.

Evaluating the progenitor cells of ovarian cancer: analysis of current animal models

“…This study provides an interesting comparison to studies of the "p53 signature", which is described as an overexpression of p53 (8,65). Point mutations in p53 often lead to stabilization and ovexpression of the protein, and if the "p53 signature" is the result of a point mutation(s) similar to that described in the study by Wang et al, it is possible that at least a subset of the adenocarcinomas observed may have originated from the oviduct (8,(64)(65)(66).…”

Roles of JNK and P53 in Taxol-Induced Apoptotic Signaling in SKOV3 Human Ovarian Cancer Cells

“…It has been well established either loss of wild type p53 function, gain of oncogenic function, or the ability to activate p53 inappropriately severely compromises the capacity for controlled cellular proliferation and growth [37]. In addition, despite the fact that both p53 and JNK have previously been shown to mediate cellular responses to the actions of a microtubule-interfering agent [10], their interrelationships have been far from clear.…”

Anti-proliferative and pro-apoptotic actions of a novel human and mouse ovarian tumor-associated gene OTAG-12: downregulation, alternative splicing and drug sensitization

“…Sixteen candidate tumor suppressor genes have been studied in OC (Bast Jr et al, 2009). EOC is a heterogeneous disease with complex pathology and more than 50% of high-grade serous-type EOCs contain p53 mutations and alterations in the retinoblastoma (RB) pathway (Corney et al, 2008;Bast Jr et al, 2009), whereas K-Ras, Pten and Wnt/b-catenin are implicated in endometrioid OC subtype (Dinulescu et al, 2005;Wu et al, 2007).…”