Tumor Specific Regulation of C-CAM Cell Adhesion Molecule in Prostate Cancer Carcinogenesis
Abstract
Loss of tumor suppressor is one of the major mechanisms that lead to tumor formation. We propose to elucidate the mechanism of loss of CEACAMI tumor suppressor expression in prostate cancer. We found that down-regulation of CEACAMI expression in prostate tumors is mainly due to transcriptional down-regulation of CEACAMI gene. We have identified three transcription factors i.e. AP-2 androgen receptor and Sp2 that are involved in the regulation of CEACAMI gene expression. The identification of Sp2 as a transcriptional suppressor of CEACAMI gene is a novel finding. We found that down-regulation of CEACAMI gene is mediated by Sp2, which is highly expressed in prostate cancer cells. Inhibitors of histone deacetylase dramatically potentiate CEACAMI expression in prostate cancer cell lines suggesting that Sp2 inhibits CEACAMI gene expression through recruitment of histone deacetylase. Thus, loss of CEACAMI 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 CEACAMI gene during tumorigenesis and this may lead to design new therapy strategies to alter tumor progression or to implement early detection and prevention strategies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA414796
Entities
People
- Sue-haw Lin
Organizations
- The University of Texas MD Anderson Cancer Center