Epigenetic regulation of coxsackie and adenovirus receptor (CAR) gene promoter in urogenital cancer cells.

Abstract

Coxsackie and adenovirus receptor (CAR) is not only a high-affinity receptor for adenovirus, but also a tumor inhibitor in both prostate and bladder cancer lines. Decreased CAR gene expression is often detected in cancer specimens; however, the mechanism(s) is still unknown. In this study, we cloned the entire CAR gene and characterized the core promoter sequence of the CAR gene. The CAR gene promoter activity correlated with the differential expression of CAR mRNA levels from several urogenital cancer cell lines, indicating that the down-regulation of CAR gene expression is mediated by transcriptional regulation. It is known that epigenetic control, such as DNA methylation and histone acetylation of chromatin structure, dictates gene expression. Data from this study indicate that the activation of the CAR gene promoter is modulated by histone acetylation, but not by DNA methylation, in urogenital cancer cells. Also, a potent cancer chemotherapeutic agent (FR901228), a histone deacetylase inhibitor, was able to induce endogenous CAR gene expression in several urogenital cancer cells. Taken together, epigenetic control of CAR gene underlies the down-regulation of this gene in urogenital cancers.

• Authors: Rey-Chen Pong, Yun-Ju Lai, Hong Chen, Takasugu Okegawa, Eugene Frenkel, Arthur Sagalowsky, Jer-Tsong Hsieh
• Journal: Cancer research (Cancer Res) Vol. 63 Issue 24 Pg. 8680-6 (Dec 15 2003) ISSN: 0008-5472 [Print] United States
• PMID: 14695181 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CLMP protein, human
• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• Receptors, Virus

Topics

• Base Sequence
• Carcinoma, Transitional Cell (genetics, metabolism)
• Cell Line, Tumor
• Cloning, Molecular
• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• Gene Expression Regulation, Neoplastic
• Humans
• Molecular Sequence Data
• Promoter Regions, Genetic
• Receptors, Virus (biosynthesis, genetics)
• Urinary Bladder Neoplasms (genetics, metabolism)