Suppression of tumourigenicity in human colon carcinoma cells by introduction of normal chromosome 1p36 region.
Development of colon carcinomas appears to be associated with inactivation of multiple tumour suppressor genes. Cytogenetic and DNA analyses of colon carcinomas have detected a high frequency of chromosome 1p deletion, which suggests the presence of a tumour suppressor gene. We therefore introduced normal human chromosome 1 into colon carcinoma COKFu cells, through microcell hybridization. Six clones of hybrid cells containing normal chromosome 1 were obtained, four of which had a small fragment of the introduced chromosome 1, including 1p36-34. The morphology of hybrid cells with chromosome 1 markedly altered to a flat shape. The cloning efficiency of all six hybrid cells in soft agar was significantly reduced, and the tumourigenicity in athymic nude mice was completely suppressed. Hybrid cells containing only the region of 1p36-34, as well as those containing intact chromosome 1, showed suppressed transformed phenotype. Furthermore, several tumourigenic revertant cells were obtained from the hybrid cells. These revertant cells had a morphology similar to that of COKFu cells, and were found to have lost the 1p36 region from the introduced chromosome 1. These results indicate that a normal chromosome 1p36 carries a tumour suppressor gene for colon carcinogenesis.
Tanaka
K
K
Department of Biochemistry, Tokyo Metropolitan Institute of Medical Science.
Yanoshita
R
R
Konishi
M
M
Oshimura
M
M
Maeda
Y
Y
Mori
T
T
Miyaki
M
M
D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D000818:Animals; D002878:Chromosomes, Human, Pair 1; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D016147:Genes, Tumor Suppressor; D006801:Humans; D006822:Hybrid Cells; D051379:Mice; D008819:Mice, Nude; D012150:Polymorphism, Restriction Fragment Length