PROSAPOSIN, A PROMOTER OF PROSTATE CARCINOGENESIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 答：具体目的：PSAP是我们实验室鉴定、克隆和鉴定的一种70 kDa的蛋白质，发现它能促进PCa细胞的生长、迁移和侵袭。小鼠PSAP基因纯合失活导致男性生殖器官萎缩和萎缩，大体病理特征包括睾丸、精囊和前列腺的大小和重量减少。对消退的前列腺组织进行组织学检查，发现存在未分化的上皮细胞。总而言之，这些数据支持PSAP在前列腺癌中的发育作用。 我们目前的数据显示，shRNA下调PSAP的表达可以显著降低PCa细胞与基底膜蛋白的粘附性，(B)蛋白水解酶(如组织蛋白酶D)的表达，以及(C)PCa细胞的迁移和侵袭特性。为了验证我们的假设，即PSAP对人前列腺癌细胞的侵袭有很大贡献，我们提出了以下具体目标： 1.明确PSAP调节PCa体外侵袭的机制。 2.确定PSAP和组织蛋白酶D在PCa细胞侵袭中的作用机制及因果关系。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A. Specific Aims: PSAP is a 70-kDa protein identified, cloned, and characterized by our laboratory and found to increase growth, migration, and invasion of PCa cells. Homozygous inactivation of the PSAP gene in mice led to shrinkage and atrophic changes in the male reproductive organs, with gross pathological features including a reduction in size and weight of the testes, seminal vesicle, and prostate gland. Histological examination of the involuted prostate tissue revealed the presence of undifferentiated epithelial cells. Collectively, these data support a developmental role for PSAP in the prostate gland. Our current data show that down modulating PSAP expression by shRNA leads to a significant reduction of (a) PCa cells adhesion to basement membrane proteins, (b) the expression of the proteolytic enzymes (e.g., Cathepsin D) and (c) migratory and invasion properties of PCa cells. To test our hypothesis that PSAP contributes substantially to the invasion of human PCa cells, we proposed the following Specific Aims: 1. Define the mechanisms by which PSAP regulates PCa invasion in vitro. 2. Determine the underlying mechanisms and the cause and effect relationship between PSAP and cathepsin D in PCa cells invasiveness.