Altered growth of human colon cancer cell lines disrupted at activated Ki-ras.
Point mutations that activate the Ki-ras proto-oncogene are presented in about 50 percent of human colorectal tumors. To study the functional significance of these mutations, the activated Ki-ras genes in two human colon carcinoma cell lines, DLD-1 and HCT 116, were disrupted by homologous recombination. Compared with parental cells, cells disrupted at the activated Ki-ras gene were morphologically altered, lost the capacity for anchorage-independent growth, grew more slowly both in vitro and in nude mice, and showed reduced expression of c-myc. Thus, the activated Ki-ras gene plays a key role in colorectal tumorigenesis through altered cell differentiation and cell growth.
Shirasawa
S
S
Department of Genetics, Kyushu University, Fukuoka, Japan.
Furuse
M
M
Yokoyama
N
N
Sasazuki
T
T
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002455:Cell Division; D003062:Codon; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007223:Infant; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009693:Nucleic Acid Hybridization; D010957:Plasmids; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D015183:Restriction Mapping; D014162:Transfection; D014407:Tumor Cells, Cultured
D003062:Codon; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas