PGC-1α在子宫内膜癌中的表达调控及其作用机制研究

Long-term no antagonstic estrogen action is a cause of endometrial cancer. Obesity is a risk factor for endometrial cancer, but the relationship between obesity and estrogen is not entirely clear. Peroxisome proliferator-activated receptorgamma co-activator factor-1α (PGC-1α) is an estrogen receptor coactivator, promoting the transcription of estrogen target genes associated with oncogenesis; on the other hand, PGC-1α is also a sensitive regulator of metabolism associated with obesity. Preliminary studies of our research group have found that expression of PGC-1α was upregulated in endometrial carcinoma cell lines; And adiponectin could downregulate PGC-1α, thus inhibit endometrial cancer cell proliferation; Moreover, adiponectin could antagonize proliferation-promoting effect of estrogen on endometrial cancer cell lines. Based on those findings, our research group will first clear the expression change and mechanism of PGC-1α under adiponectin effection; followed by the use of recombinant DNA technology, observed proliferation and invasion of endometrial cancer cells under PGC-1α plasmid effection, and to explore the role above if related to its auxiliary activate ER target gene transcription; additionally, our project will also clarify the relation of downregulated PGC-1α under adiponection with ER signaling pathway. These findings are still blank in the international arena, its expected to enrich the understanding of the pathogenesis of endometrial cancer.

长期无拮抗雌激素作用是子宫内膜癌致病因子,而肥胖是子宫内膜癌发病的一个高危因素，但两者关系不完全清晰；过氧化物酶体增殖物激活受体γ共激活因子-1α(PGC-1α)是雌激素受体辅激活因子，促进雌激素靶基因转录,与肿瘤发生有关；同时也是代谢的敏感器和调节器,与肥胖相关。课题组前期发现，子宫内膜癌细胞株PGC-1α表达上调；脂联素可下调PGC-1α,拮抗雌激素对内膜癌细胞株的增殖促进作用，因此认为PGC-1α可能受脂联素调节从而影响子宫内膜癌发生、发展。本项目首先明确脂联素作用下PGC-1α表达的变化及可能机制；其次运用基因技术，观察不同表达状态下PGC-1α对子宫内膜癌细胞株增殖及侵袭的作用，并探讨其作用是否与辅助激活ER靶基因转录有关。本项目预期的研究结果将丰富人们对子宫内膜癌发病机制的认识。