| First Author | Pan J | Year | 2015 |
| Journal | Sci Rep | Volume | 5 |
| Pages | 14958 | PubMed ID | 26468779 |
| Mgi Jnum | J:257401 | Mgi Id | MGI:6101962 |
| Doi | 10.1038/srep14958 | Citation | Pan J, et al. (2015) Elevation of omega-3 Polyunsaturated Fatty Acids Attenuates PTEN-deficiency Induced Endometrial Cancer Development through Regulation of COX-2 and PGE2 Production. Sci Rep 5:14958 |
| abstractText | Endometrial cancer is one of the most common gynecologic malignancies. Phosphatase and tensin homologue (PTEN)-mutation is frequently identified in endometrial cancer patients. Although high dietary intake of omega-3 polyunsaturated fatty acids (PUFAs) has been associated with reduced risk of endometrial cancer, the underlying mechanisms is still unknown. To this end, we evaluated the impact of omega-3 PUFAs using several endometrial cancer cellular and animal models. While ~27% and 40% of heterozygotic PTEN mutant mice developed endometrial cancer and atypical complex hyperplasia, respectively, none of the PTEN(+/-) mice developed cancer when we overexpressed an mfat-1 transgene, which allowed endogenous production of omega-3 PUFAs. Fish oil-enriched diet or expression of mfat-1 transgene significantly inhibited the growth of xenograft tumor derived from RL95-2 cells bearing a PTEN null mutation. At cellular level, omega-3 PUFAs treatment decreased the viability of RL95-2 cells, AKT phosphorylation, and cyclin D1 expression. These molecular events are primarily mediated through reduction of cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production. Exogenous PGE2 treatment completely blunted the impact of omega-3 PUFAs on endometrial cancer. Thus, we revealed the direct inhibitory effects of omega-3 PUFAs on endometrial cancer development and the underlying mechanisms involving reduction of COX-2 and PGE2. |
