PROSAPOSIN, A PROMOTER OF PROSTATE CARCINOGENESIS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 A.具体目标：PSAP是我们实验室鉴定、克隆和表征的70-kDa蛋白，并且发现其增加PCa细胞的生长、迁移和侵袭。小鼠PSAP基因的纯合失活导致雄性生殖器官萎缩和萎缩性变化，大体病理学特征包括睾丸、精囊和前列腺的大小和重量减少。退化的前列腺组织的组织学检查显示存在未分化的上皮细胞。总的来说，这些数据支持PSAP在前列腺中的发育作用。 我们目前的数据显示，通过shRNA下调PSAP表达导致（a）PCa细胞与基底膜蛋白的粘附显著减少，（B）蛋白水解酶（例如，组织蛋白酶D）和（c）PCa细胞的迁移和侵袭特性。为了检验我们的假设，即PSAP实质上有助于人PCa细胞的侵袭，我们提出了以下具体目的： 1.定义PSAP调节体外PCa侵袭的机制。 2.探讨PSAP和组织蛋白酶D在PCa细胞侵袭中的作用机制及其因果关系。

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.