A NOVEL CANDIDATE ONCOGENE, MCT-1, IS INVOLVED IN CELL-CYCLE PROGRESSION

Using the arbitrarily primed-PCR (AP-PCR) assay to detect genetic abno rmalities that occur in a panel of lymphoid cell Lines, we identified an amplified stretch of genomic DNA that contained a putative open rea ding frame, Northern blot analysis with this genomic clone revealed wi despread low level expression in normal human tissue. The full cDNA se quence was obtained with no significant homology to any known genes in the genome database, We termed this novel gene with multiple copies i n a T-cell malignancy as MCT-I, MCT-I was localized to the long arm of chromosome Xq22-24 by flourescence in situ hybridization analysis. Al though there was no significant homology at the primary sequence level , there was a limited degree of amino acid homology with a domain of c yclin H that appears to specify protein-protein complexes. This relati onship between MCT-1 and cyclin H implied a potential role for MCT-1 i n cell cycle regulation. Overexpression of MCT-I increased the prolife rative rate of cells by decreasing the length of the G(1) phase withou t a reciprocal increase in the S and G(2)-M phases. Recent work has es tablished the role of cell cycle regulatory molecules in the developme nt of certain human malignancies, Therefore, we investigated the trans forming ability of MCT-I overexpression using soft agar growth assays and demonstrated that only MCT-I-overexpressing cells were able to est ablish colonies. Taken together, MCT-1 is a novel candidate oncogene w ith homology to a protein-protein binding domain of cyclin H.