Abstract
Abstract INTRODUCTION: Cancer progression and tumorigenesis have been linked to alterations in cellular metabolic pathways of lipid and cholesterol synthesis in many cancers. Increased levels of cholesterol esters (CE) have been reported in breast cancer, leukemia, glioma and prostate cancer, but not exploited in detail in ovarian and endometrial cancers. Inside cells, excess free cholesterol is esterified by acyl-CoA cholesterol acyltransferase (ACAT) and stored as cholesteryl ester (CE) in lipid droplets (LDs). Cholesteryl ester accumulation may be a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway as observed in pancreatic cancer. In the present study, we focused on the role of ACAT and cholesterol esters in altered cholesterol metabolism in ovarian/endometrial cancer cell lines. METHODS: We studied the effect of abrogation of cholesterol esterification either by an ACAT-1 inhibitor/shRNA knockdown or via inhibition of PI3K/AKT/mTOR pathways and subsequent effect on ovarian/endometrial cancer cells proliferation, invasion, cell migration and tumorigenesis. The expression of ACAT was studied at the protein and mRNA levels in a panel of ovarian/ endometrial cancer cell lines and also in normal and ovarian cancer clinical samples. ACAT expression was assessed by western blotting, ELISA, quantitative RT-PCR and immunostaining techniques. RESULTS: Our results reveal an elevated expression of ACAT-1 at both protein and mRNA levels in ovarian and endometrial cancer cell lines as compared to primary cells. Our results also provide preliminary data on involvement of ACAT and cholesterol esters in the progression and metastasis of ovarian cancer. CONCLUSION: These studies may aid in the development of new biomarkers or treatment targets for ovarian/endometrial cancer. Citation Format: Vijayalakshmi N. Ayyagari, Xinjia Wang, Laurent Brard. Studies on role of acyl-CoA cholesterol acyltransferase (ACAT) expression in ovarian/endometrial cancer progression - An invitro study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4416. doi:10.1158/1538-7445.AM2017-4416
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