AN ALTERNATIVELY SPLICED FORM OF APOBEC-1 MESSENGER-RNA IS OVEREXPRESSED IN HUMAN COLON-CANCER

Background & Aims: Apobec-1 is an RNA-specific cytidine deaminase whos e forced overexpression in transgenic animals is associated with hepat ic carcinogenesis. Apobec-1 messenger RNA (mRNA) undergoes alternative splicing, generating a catalytically inactive peptide, apobec-T. We h ave examined apobec-1 gene expression in human gastrointestinal tumors and in colon cancer-derived cell lines. Methods: Levels of the full-l ength (apobec-1) and alternatively spliced (apobec-T) mRNAs were measu red by RNase protection assay, and apobec-T distribution was determine d by immunocytochemical localization. Results: Apobec-1 mRNA was detec table in normal and colon cancer tissue, metastatic nodules, and certa in colon cancer-derived cell lines. Apobec-T mRNA abundance was increa sed an average of 3.5-fold in colon cancers compared with paired contr ol tissue (range, 0.5-14-fold). Immunocytochemical analysis showed apo bec-T expression in normal fetal and adult colon and in gastric and sm all intestinal adenocarcinomas, colonic tubular adenomas, and both pri mary and metastatic colonic tumors. Overexpression of apobec-T in a te tracycline-responsive cell line decreased cellular proliferation. Conc lusions: Apobec-T is expressed in normal, adenomatous, and cancerous g astrointestinal tissues, and levels of the mRNA encoding this peptide are significantly increased in colon cancer. Although its relationship to colon carcinogenesis has not been defined, the regulated overexpre ssion of apobec-T is associated with an altered growth phenotype.