Molecular and genetic basis of epithelial ovarian cancer with special reference to prostaglandin-PPAR signaling.
Epithelial ovarian cancers (EOC) are marked by rapid solid tumor growth and spread, resulting in a high patient mortality rate. Indeed, EOC is the fourth-leading cause of cancer death in the United States. Little is known about the early stages of the disease and the underlying causes, making it difficult to diagnose EOC in a timely manner. Cox-2 is implicated in a variety of cancers, but until recently, the role of Cox-1 was unclear. We showed that human EOC overexpresses Cox-1, generating PGI2 and PGE2 as major prostanoids. Similarly, mouse models of EOC exhibit overexpression of Cox-1 and PGI2.
Both PGI2 and PGE2 can interact with PPARδ, which has been implicated in tumorigenesis (although the pathway is unclear). Our lab has shown that PPARδ is highly expressed in both mouse and human EOC tumors and that inhibiting PPARδ activity can reduce tumor growth. We also demonstrated that aspirin, a nonselective Cox inhibitor, compromises PPARδ function, providing a possible treatment option.