Aurora-A Oncogene in Human Ovarian Cancer
Abstract
During past year, we have demonstrated that Aurora-A protects ovarian cancer cells from apoptosis induced by chemotherapeutic agent and activates Akt pathway in a p53-dependent manner. Ectopic expression of Aurora-A renders cells resistant to cisplatin (CDDP), etoposide and paclitaxel-induced apoptosis and stimulates Akt1 and Akt2 activity in wild-type p53 but not p53-null ovarian cancer cells. Aurora-A inhibits cytochrome C release and Bax conformational change induced by CDDP. Knockdown of Aurora-A by RNAi sensitizes cells to CDDP-induced apoptosis and decreases phospho-Akt level in wild-type p53 cells. Reintroduction of p53 decreases Akt1 and Akt2 activation and restores CDDP sensitivity in p53-null but not p53-null-Aurora-A cells. Inhibition of Akt by small molecule inhibitor, API-2, overcomes the effects of Aurora-A-on cell survival and Bax mitochondrial translocation. In addition, we have identified several Aurora-A inhibitors by screening ChemDiv library. Moreover, we generated MISIIR-Aurora-A and MMTV-Aurora-A transgenic mice. While MISIIR-Aurora-A mice failed to develop ovarian tumor, MMTV-Aurora-A mice exhibited ductal carcinoma in situ.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2006
- Accession Number
- ADA462676
Entities
People
- Jin Q. Cheng
Organizations
- University of South Florida