PROSAPOSIN, A PROMOTER OF PROSTATE CARCINOGENESIS

点击翻译按钮获取中文摘要

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.