Ovarian cancer is a prevalent cause of death in women, and progressive stages of this disease are hallmarked by accumulation of ascites fluid in the abdominal cavity. Analysis of ascites fluid from ovarian cancer patients has identified significant amounts of acyl lysphospholipids, mainly lysophosphatidic acid (LPA), and alkyl ether lipids, which have been indicated in stimulating malignancy in ovarian cancer. Phospholipase D (PLD) has a potential role in promoting malignancy in ovarian cancer, as LPA can be formed from phosphatidic acid (PA), a product of the PLD hydrolytic reaction. Furthermore, ovarian cancer cells expressing the activated form of the Akt kinase produce and secrete large amounts of LPA. The primary purpose of this research is to determine the relationships among Akt activation, PLD activation, bioactive lysophospholipid production, and malignancy in ovarian cancer. This will be done by manipulating Akt activity in ovarian cancer cells, and measuring the effects of the alteration on LPA production and proliferation in the cells. The desired long-term goal is to understand the biochemical heterogeneity of lipid growth factor production in ovarian cancer. As an important concurrent study, the importance of alkyl ether lipid synthesis on proliferation of ovarian cancer cells will be determined by controlling levels of alkyl DHAP synthase, the initial enzyme involved in alkyl ether lipid synthesis. The transfected cells will be used to determine if changes in alkyl ether lipid synthesis alter proliferation.
| Saunders, Jerry A; Rogers, LeAnn C; Klomsiri, Chananat et al. (2010) Reactive oxygen species mediate lysophosphatidic acid induced signaling in ovarian cancer cells. Free Radic Biol Med 49:2058-67 |
