Methylthioadenosine phosphorylase (MTAP) is known as a ubiquitously expressed house keeping gene important in biochemical salvage processes. The MTAP gene is localized on the human chromosomal region 9p21, a region often deleted in
cancer. Recently, several groups including our own have shown that MTAP serves as a tumour suppressor gene. The aim of this study was to analyse the role of MTAP in colon
carcinoma and normal colon epithelium and the regulation of gene expression. To examine MTAP
RNA and
protein expression, we screened six colon
carcinoma cell lines and human primary colon epithelial cells by RT-PCR and immunoblotting. MTAP expression was confirmed in vivo by immunohistochemical staining of normal colon tissue compared to
adenoma and colon
carcinoma. Interestingly, we found strong MTAP
mRNA and
protein expression by colon
carcinoma cell lines but no expression by colonic epithelial cells. To analyse the regulation of MTAP expression, promoter studies were performed and revealed control of MTAP expression by LEF/TCF/
beta-catenin. Furthermore, we demonstrated a significant correlation between MTAP
protein expression and tumour progression as the intensity of MTAP
protein staining increased from normal tissue to
carcinoma. In addition, the recently postulated association between MTAP activity and
interferon (IFN) sensitivity was confirmed in colon epithelial cells showing only little response to IFN-gamma, in contrast to the
carcinoma cell lines. In summary, these data indicate for the first time that MTAP is not expressed in normal human colonic epithelium but is strongly upregulated in colon
carcinoma. This finding may be of clinical significance concerning the homeostasis of normal colon epithelium and potential treatment of colon
carcinoma.