[Analysis of molecular mechanism in colorectal tumorigenesis].
Genetic alterations of Ki-ras gene, p53 gene, and DCC gene were analyzed in human colon cancer cell lines (HCCLs). On the basis of these analyses, a HCCL (HCT116)-human chromosome 18 hybrids, and targeted cell lines that were disrupted at the activated Ki-ras gene in HCCLs (HCT116 and DLD-1), were established. Tumorigenicity and expression of c-myc gene were investigated in these cell lines, respectively. 1. Point mutations of Ki-ras gene, p53 gene, and insertion mutations of DCC gene were detected in 10 out of 18 HCCLs, 8 out of 15 HCCLs, and 3 out of 16 HCCLs, respectively. 2. HCT116-chromosome 18 hybrids were morphologically similar to the parental line, and were not suppressed for tumorigenicity in vitro, but they produced slowly growing tumors in nude mice compared with the growth of the parental line. 3. The targeted cell lines that were disrupted at the activated Ki-ras gene were morphologically altered and lost neoplastic phenotypes, including tumorigenicity in nude mice and anchorage-independent growth. Furthermore, expression of c-myc gene in these clones was much reduced compared with findings in the parental line, regardless of their growth rates.
Shirasawa
S
S
Department of Genetics, Kyushu University, Fukuoka.
D000818:Animals; D002678:Chimera; D002887:Chromosomes, Human, Pair 18; D015179:Colorectal Neoplasms / Q000235:genetics*; D016163:Genes, DCC; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D014407:Tumor Cells, Cultured