Suppression of tumorigenicity and invasiveness of colon carcinoma cells by introduction of normal chromosome 8p12-pter.

The development of human colon carcinomas is associated with a number of genetic alterations. A high frequency of deletion of the short arm of chromosome 8 at a late stage of colon carcinogenesis was detected by DNA analysis of colon carcinomas, which suggests the presence of a tumor suppressor gene. We therefore, introduced normal human chromosome 8 into colon carcinoma cells that showed allele loss on 8p21, through microcell hybridization. Five clones of hybrid cells were obtained from independent experiments. Three hybrids exhibited morphological alteration and suppressed tumorigenicity in the subcutis of nude mice, but the other two did not. The difference between the two types of hybrids was the region of the introduced normal chromosome 8: Three hybrids exhibiting morphological alteration and suppressed tumorigenicity had the entire region of the introduced chromosome 8, whereas the other two, exhibiting no change, lacked 8p12-pter from the introduced chromosome. Furthermore, the invasiveness of the hybrids with suppressed tumorigenicity was reduced to one-fifth of that of the parental cells. These results indicate that 8p12-pter carries a gene that contributes to suppression of both tumorigenicity and invasiveness of colon carcinomas.