Lyn催化半乳凝素-3磷酸化增强雄激素非依赖前列腺癌抗凋亡的机制研究

探讨雄激素非依赖前列腺癌（AIPC）的特异治疗靶点及其作用机制对前列腺癌的临床治疗具有重要意义。文献报道，非受体酪氨酸激酶Lyn是AIPC的潜在治疗靶点。前期实验发现：Lyn高表达增强了AIPC细胞的抗凋亡能力；Lyn能够催化凋亡抑制蛋白半乳凝素-3（Gal-3）酪氨酸磷酸化，并与AIPC的抗凋亡能力相关。据此，本项目提出假设“Lyn通过催化Gal-3酪氨酸磷酸化增强AIPC的抗凋亡能力”。.本项目拟从以下方面研究：1）分子水平研究Lyn催化Gal-3酪氨酸磷酸化的生物学活性；2）细胞水平研究Lyn催化Gal-3磷酸化增强AIPC抗凋亡能力的机制；3）动物水平验证Lyn催化Gal-3磷酸化增强AIPC体内抗凋亡的作用及机制。本项目首次探讨Lyn在AIPC进程中的抗凋亡功能及其机制，研究结果将为AIPC的靶点治疗和药物开发提供可靠的理论依据。

It is significant to study the specific therapeutic targets of androgen independent prostate cancer (AIPC) and their related mechanisms for the clinical treatment of prostate cancer. Lyn kinase is a potential therapeutic target of AIPC according to the literatures. Our previous studies have shown that the over-expression of Lyn enhances the anti-apoptosis activity of AIPC. And, Lyn could catalyze the phosphorylation of galectin-3, which is related to the anti-apoptosis activity of AIPC. Accordingly, we propose that Lyn enhances the anti-apoptosis activity of AIPC through catalyzing the phosphorylation of galectin-3. In order to confirm the hypothesis, we will carry out the following studies: 1) to study the phosphorylation of Gal-3 catalyzed by Lyn in molecular level; 2) to illuminate the mechanism of Lyn enhancing the anti-apoptosis activity of AIPC through catalyzing the phosphorylation of galectin-3 in cellular level; 3) to confirm the activity and mechanism of Lyn enhancing the anti-apoptosis activity of AIPC in vivo through catalyzing the phosphorylation of galectin-3 in animal level. This project will be the first time to explore the anti-apoptosis function and mechanism of Lyn in the process of AIPC, and the results will provide the reliable theoretical evidence for the target treatment and medicine development of AIPC.