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 by the rat liver oncofetal cDNA TA1 and the human lymphocyte activation gene E16 display a high degree of homology with coding regions recently identified in Schistosoma mansoni and Caenorhabditis elegans. Previous studies showed that up-regulation of TA1/ E16 expression was associated with rat hepatocarcinogenesis and human tumor cell lines; therefore, we analyzed several primary human tumors including a panel of 20 colon carcinomas to evaluate the relationship of TA1/E16 RNA and protein expression to neoplasia. A 4.0-kb transcript was detected in all but one colorectal carcinoma but not in normal colon or specimens of inflammatory bowel disease. Steady-state TA1/E16 mRNA levels varied considerably between carcinomas and did not correlate simply with mitotic index, modified Dukes' stage, or tumor size. TA1/E16 message also was detected in adenocarcinomas from breast, endometrium, salivary gland, and esophagus. Western blot analysis using antibodies against TA1/E16-deduced peptides identified major reactive bands of approximately 35 and 19 kDa in neoplasms but not in normal tissue. Immunoperoxidase staining localized the protein primarily to the supranuclear region of colon carcinoma cells, whereas normal epithelial cells were negative. Heterogeneous staining was found in villous adenomas with focal intramucosal adenocarcinoma but was negative in tubular adenomas, suggesting that expression of TA1/E16 may correlate with neoplastic progression in the colon. Up-regulation of this gene in various human cancers suggests a common role in the carcinogenic process and possible application as a tumor marker.
Department of Pathology, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island 02903, USA.
D A
DA
Wolf
S
S
Wang
M A
MA
Panzica
N H
NH
Bassily
N L
NL
Thompson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D026905:Amino Acid Transport Systems; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000235:genetics*; D003110:Colonic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D003111:Colonic Polyps / Q000737:chemistry; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012550:Schistosoma mansoni / Q000201:enzymology*; D017386:Sequence Homology, Amino Acid
D026905:Amino Acid Transport Systems; D000951:Antigens, Neoplasm; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C031192:oncofetal antigens