Pro-lipogenic Action of Lysophosphatidic Acid in Ovarian Cancer
Revised annual rept. 1 July 2011-30 June 2012
VIRGINIA COMMONWEALTH UNIV RICHMOND
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The objective of the project is to determine the role of endogenous lysophosphatidic acid LPA in lipogenesis and metabolic abnormalities of ovarian cancer cells. During the first year of the funding support, we have pursued the specific aims and subaims as originally planned. The major discoveries include identification of LPA as a primary serum constituent to promote lipogenesis, role of iPLA2b in cell growth and potentially lipogenesis, downregulation of AMPATP ratio by LPA to inactivate AMPK, involvement of exogenous fatty acids via b oxidation to enhance LPA-induced cell growth, and LPA activation of the cholesterol rate-limiting synthesizing enzyme HMG-CoA reductase and cholesterol synthesis in ovarian cancer cells. Some of these results have been published in our recent paper Journal of Biological Chemistry, 287 24990-25000, 2012. The details of the unpublished results were presented and discussed in this report under each of the specific aims. We have also developed necessary reagents or learnt important techniques for the rest of the tasks. We expect to accomplish the project objectives within the 2nd year of the support with no major difficulty or change in research directions.
- Medicine and Medical Research