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 cells. Conversion of these cells to a tumorigenic phenotype with chemical mutagens did not increase mutations in hot spots or other conserved regions of p53 or H-ras genes. Investigation of the tumorigenic conversion using an expression library resulted in isolation of a previously unidentified gene, CATR1, located on the long arm of chromosome 7 at band approximately q31-32. Evidence for the involvement of this gene in conversion to tumorigenicity was demonstrated by introduction of a eukaryotic expression CATR1 construct into SCC83-01-82 cells. Transfection with the antisense construct reduced the expression of CATR1 in tumors formed by the transfected cells, suggesting that the antisense suppression of endogenous CATR1 expression appeared to be sufficient for tumorigenic conversion. These results are consistent with previous reports of cytogenetic analyses of tumors, that 7q31-32 contains a gene(s) with tumor suppressor activity; CATR1 is a candidate for this putative suppressor gene.