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-expressed gene) initially selected from various human libraries and completed by 5' rapid amplification of cDNA ends (RACE) PCR is described. The original cDNA clone was extracted from an expression library constructed from a human tumoral brain. This library was screened with an antibody 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 sequence shows no significant similarity with any of the gene sequences collected in the various DNA data bases. The translation of the larger open reading frame leads to a putative protein of 1972 amino acids (molecular mass = 218453 Da). Hybridization analyses on Southern blot and on metaphase chromosomes indicate that this gene is present as a single copy in the genome and is localized on the short arm of chromosome 11. ch-TOG transcripts are present in several human tissues. Over-expression of ch-TOG in neoplastic liver and colon compared with the corresponding normal corresponding tissues is demonstrated. The level of the expression of ch-TOG transcripts was also studied in the various differentiation stages of the human colonic adenocarcinoma cell line Caco-2.