MARC Predoctoral Fellowship Program

自噬的过程是蛋白质和其他溶酶体降解的复杂分解代谢过程。 亚细胞成分。它对正常的生长控制很重要，在许多癌症中是有缺陷的。 Beclin 1基因是第一个被发现参与自噬的哺乳动物基因。Beclin 1基因的单等位基因缺失 在40-75%的人类散发性乳腺癌、卵巢癌和前列腺癌中发现了这种基因。纯合子Beclin 1基因敲除的小鼠对胚胎是致命的，而杂合子Beclin 1基因敲除的小鼠则发育出不同的 肿瘤。这一小鼠遗传结果提供了令人信服的证据，证明自噬在 预防肿瘤的发生。然而，为什么Beclin 1基因和自噬对肿瘤至关重要 镇压仍不得而知。自噬的重新激活可能是一种有效的癌症治疗方法 策略。初步数据表明，模拟的Beclin 1突变体的外源表达 MCF7细胞中的结构性磷酸化导致自噬的激活。此工具将用于 建立细胞和动物模型来描述重新激活自噬的后果。

The process of autophagy is a complex catabolic program for lysosomal degradation of proteins and other subcellular constituents. It is important for normal growth control and is defective in a number of cancers. Beclin 1 gene is the first mammalian gene identified involved in autophagy. Mono-allelic deletions of Beclin 1 gene are identified in 40 -75% of human sporadic breast, ovarian and prostate cancers. Homozygous Beclin 1 knockout mice are embryonic lethal, while the heterozygous Beclin 1 knockout mice develop various tumors. This mouse genetic result provides compelling evidence that autophagy plays an important role in preventing tumorigenesis. However, exactly why the Beclin 1 gene and autophagy are critical for tumor suppression remains unknow. The re-activation of autophagy may be an efficient cancer therapeutic strategy. Preliminary data indicates that exogenous expression of the Beclin 1 mutant which mimics constitutive phosphorylation in MCF7 cells results in the activation of autophagy. This tool will be used to consfruct cellular and animal models to characterize the consequence of re-activating autopahgy.