脂质代谢调控基因SRB1和ABCA1在前列腺癌恶性进展中的作用和机制研究

项目名称： 脂质代谢调控基因SRB1和ABCA1在前列腺癌恶性进展中的作用和机制研究

项目编号： No.81502201

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 鲁欣

作者单位： 中国人民解放军第二军医大学

项目金额： 18万元

中文摘要： 恶性肿瘤的重要标志是细胞能量代谢调控网络紊乱，多种肿瘤包括前列腺癌乳腺癌早期均发现脂质代谢的激活。我们在前期对前列腺癌根治手术组织标本的研究发现，不饱和脂肪酸胆固醇酯在癌组织中的含量明显升高，且其含量与前列腺癌的恶性程度，侵袭进展趋势一致。进一步研究发现前列腺癌的临床恶性进展与胆固醇酯的含量密切相关，但单一基因的变化无法直接与恶性程度相关联。SRB1和ABCA1作为调控细胞胆固醇代谢平衡的重要分子，在这一代谢紊乱中起到重要作用。本项目将主要研究其在前列腺癌中的表达及与前列腺癌进展的关系；模拟高胆固醇酯蓄积肿瘤微环境，检测引起胆固醇酯蓄积相关基因和蛋白表达水平，确定参与前列腺癌恶性进展的关键基因和蛋白表达变化；探讨抑制胆固醇酯蓄积降低前列腺癌侵袭转移可能。从而可能在前列腺癌发病机制，分子分型方面提供新的证据，为个体化治疗提供新的可行途径。

中文关键词： 前列腺癌；脂质代谢

英文摘要： SRB1 (scavenger receptor class B member 1) functions as a receptor for high-density lipoprotein facilitating the uptake of cholesteryl esters, and ABCA1 (ATP-binding cassette transporter member 1 of human transporter sub-family ABCA) also known as the cholesterol efflux regulatory protein (CERP) is a major regulator of cellular cholesterol and phospholipid homeostasis. A hallmark of malignant tumors is disorder of regulatory networks of cellular energy metabolism. Among a variety of malignant tumors including breast cancer and prostate cancer, lipid metabolism was found activated. Previous researches in tissue samples of radical prostatectomy showed that levels of poly-unsaturated fatty acids cholesterol ester are significantly increased in tumor tissues compared with adjacent benign prostate tissues. Furthermore, the ratios of levels in tumor tissues compared with adjacent benign prostate tissues are consistent with degree of invasion and malignancy. Clinical evaluation of malignancy of prostate cancer is related to the content of cholesterol ester, but variations of a single gene cannot directly associate with degree of malignancy. SRB1 and ABCA1 play an important role in this metabolic disorder. Based on previous studies and literatures, the project will focus on the expression of genes related to lipid metabolisms and relationship with progression of prostate cancer. Through simulating tumor microenvironment of high cholesterol, we plan to detect expression of genes and proteins which may contribute to accumulation of cholesterol ester. We plan to analyze the possible mechanism of epithelial-mesenchymal transition by altering tumor microenvironment and identify the key genes involved in microenvironment changes. The project also aim to investigate the possible inhibition of tumor invasion and metastasis by reducing accumulation of cholesteryl ester. Through above plans, we hope to provide new evident involving the pathogenesis and progression of prostate cancer, molecular typing, and find an alternative tool to individualized therapy.

英文关键词： prostate cancer;lipid metabolism