EXPRESSION OF A HIGHLY CONSERVED ONCOFETAL GENE, TA1 E16, IN HUMAN COLON-CARCINOMA AND OTHER PRIMARY CANCERS - HOMOLOGY TO SCHISTOSOMA-MANSONI AMINO-ACID PERMEASE AND CAENORHABDITIS-ELEGANS GENE-PRODUCTS/

The peptides encoded bg the rat liver oncofetal cDNA TAI and the human lymphocyte activation gene E16 display a high degree of homology with coding regions recently identified in Schistosoma mansoni and Caenorh abditis elegans. Previous studies showed that up-regulation of TA1/E16 expression was associated with rat hepatocarcinogenesis and human tum or cell lines; therefore, we analyzed several primary human tumors inc luding a panel of 20 colon carcinomas to evaluate the relationship of TA1/E16 RNA and protein expression to neoplasia. A 4.0-kb transcript w as detected in all hut one colorectal carcinoma hut not in normal colo n or specimens of inflammatory bowel disease. Steady-state TA1/E16 mRN A levels varied considerably between carcinomas and did not correlate simply with mitotic index, modified Dukes' stage, or tumor size, TA1/E 16 message also was detected in adenocarcinomas from breast, endometri um, salivary gland, and esophagus. Western blot analysis using antibod ies against TA1/E16-deduced peptides identified major reactive bands o f approximately 35 and 19 kDa in neoplasms but not in normal tissue. I mmunoperoxidase staining localized the protein primarily to the supran uclear region of colon carcinoma cells, whereas normal epithelial cell s were negative. Heterogeneous staining was found in villous adenomas with focal intramucosal adenocarcinoma but was negative in tubular ade nomas, suggesting that expression of TA1/E16 may correlate with neopla stic progression in the colon. Up-regulation of this gene in various h uman cancers suggests a common role in the carcinogenic process and po ssible application as a tumor marker.