The Role of Cyclin E and its Lower Molecular Forms in the Oncogenesis of Ovarian Cancer and its Predictive Value in Patients with Early Stage Ovarian Tumor
Final rept. 1 Apr 2003-31 Mar 2007
M D ANDERSON CANCER CENTER HOUSTON TX
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The deregulation of cell cycle checkpoints, with loss of regulation at the G1S transition, has been shown to play an important role in the transformation to a malignant phenotype. Our studies have focused on cyclin E, which appears in late G1 and flanks the restriction point .We hypothesize that alterations of cyclin E in ovarian cancer cells contributes to the oncogenesis of ovarian tumors and negatively impacts outcome in patients with Stage I-III cancer. In this proposal we will i develop a comprehensive ovarian cell line model for characterization of the role of cyclin E in ovarian cancer, ii delineate the role of cyclin E and its tumor specific LMW forms in the development of malignant phenotype in vitro and in nude mice. iii establish the prognostic value of the hyperactive forms of cyclin E in patients with Stage I-III ovarian cancer and iv examine the biochemical significance of the LMW forms of cyclin E in tumor specimens. The results from our studies will provide much needed information about the molecular biology of ovarian carcinoma and may open new avenues for the development of targeted therapies.
- Medicine and Medical Research