Tumor Specific Regulation of C-CAM Cell Adhesion Molecule in Prostate Cancer Carcinogenesis

摘要

Down-regulation of carcinoembryonic antigen-related cell adhesion molecule (CEACAM1) tumor suppressor gene expression is common in several malignancies including prostate. The mechanism that mediates this down- regulation is not known. We propose to elucidate the mechanism of loss of CEACAM1 tumor suppressor expression in prostate cancer. We found that down- regulation of CEACAM1 expression in prostate tumors is mainly due to transcriptional down-regulation of CEACAM1 gene. We have identified two transcription factors, i.e. AP-2 and androgen receptor, that are involved in the up-regulation of CEACAM1 gene expression and one transcription repressor, i.e. Sp2, that specifically down-regulates CEACAM1 promoter activity in tumor cells. The identification of Sp2 as a transcriptional suppressor of CEACAM1 gene is a novel finding. We found that Sp2 represses CEACAM1 gene expression by recruiting histone deacetylase activity to the CEACAM1 promoter. Thus, loss of CEACAM1 tumor suppressor gene expression in prostate cancer is due to aberrant chromatin acetylation. Results from this study will allow us to better understand the regulation of CEACAM1 gene during tumorigenesis and this may lead to design new therapy strategies to alter tumor progression or to implement early detection and prevention strategies.