Novel Diagnostic and Therapeutic Marker for Prostate Cancer

摘要

This is a final report correlating loss of SSeCKS (Src Suppressed C Kinase Substrate; pronounced essex) expression with increased metastatic potential in prostate cancer. The expression of SSeCKS, and its human orthologue, Gravin, is severely downregulated in human and rat prostate cancer cell lines compared to immortalized, untransformed prostate epithelial cell lines or prostate tissue sections from normal patients or patients with benign prostatic hypertrophy or low-grade prostate cancers (Gleason < 5) SSeCKS/Gravin staining in advanced, undifferentiated human prostate tissue sections (Gleason > 6) was severely downregulated. The regulated re-expression of SSeCKS in prostate cancer cell lines suppressed growth and induced differentiation, marked by cell flattening, filopodia formation, cell-cell adhesion and the loss of anchorage- independent growth. In nude mice, SSeCKS re-expression severely decreased the formation of lung metastases. These data strongly suggest that SSeCKS/Gravin encode prostate metastasis-suppressors.