CHARACTERIZATION OF THE CDNA AND PATTERN OF EXPRESSION OF A NEW GENE OVER-EXPRESSED IN HUMAN HEPATOMAS AND COLONIC TUMORS

A cDNA clone of 6.449 kb ch-TOG (for colonic and hepatic tumor over-ex pressed gene) initially selected from various human libraries and comp leted by 5' rapid amplification of cDNA ends (RACE) PCR is described. The original cDNA clone was extracted from an expression library const ructed from a human tumoral brain. This library was screened with an a ntibody raised against the cytochrome P450tu that was shown to be over -expressed in chemically induced mouse hepatic tumors. Using this cDNA as a probe, a full-length cDNA was characterized. its nucleotide sequ ence shows no significant similarity with any of the gene sequences co llected in the various DNA data bases. The translation of the larger o pen reading frame leads to a putative protein of 1972 amino acids (mol ecular mass = 218453 Da). Hybridization analyses on Southern blot and on metaphase chromosomes indicate that this gene is present as a singl e copy in the genome and is localized on the short arm of chromosome 1 1. ch-TOG transcripts are present in several human tissues. Over-expre ssion of ch-TOG in neoplastic liver and colon compared with the corres ponding normal corresponding tissues is demonstrated. The level of the expression of ch-TOG transcripts was also studied in the various diff erentiation stages of the human colonic adenocarcinoma cell line Caco- 2.