MALIGNANT CONVERSION OF HUMAN-CELLS BY ANTISENSE CDNA TO A PUTATIVE TUMOR-SUPPRESSOR GENE

A cell line, SCC83-01-82, derived from a human oral squamous carcinoma , was non-tumorigenic in nude mice, a characteristic of premalignant c ells. Conversion of these cells to a tumorigenic phenotype with chemic al mutagens did not increase mutations in hot spots or other conserved regions of p53 or H-ras genes, Investigation of the tumorigenic conve rsion using an expression library resulted in isolation of a previousl y unidentified gene, CATR1, located on the long arm of chromosome 7 at band similar to q31-32, Evidence for the involvement of this gene in conversion to tumorigenicity was demonstrated by introduction of a euk aryotic expression CATR1 construct into SCC83-01-82 cells, Transfectio n with the antisense construct reduced the expression of CATR1 in tumo rs formed by the transfected cells, suggesting that the antisense supp ression of endogenous CATR1 expression appeared to be sufficient for t umorigenic conversion, These results are consistent with previous repo rts of cytogenetic analyses of tumors, that 7q31-32 contains a gene(s) with tumor suppressor activity; CATR1 is a candidate for this putativ e suppressor gene.