Role of activated c-H-ras oncogene in the induction and progression of immortal liver epithelial cell lines derived from normal C3H mice.
The nature of 15 immortal mouse liver epithelial cell (MLEC) lines established from normal C3H mice was investigated specifically in terms of ras oncogene activation. Neither transforming activity nor point mutation within codon 61 of c-H-ras could be demonstrated in any of the cell lines by DNA transfection in a NIH/3T3 cell system or by the direct sequencing method after polymerase chain reaction, respectively. Acrylamide gel migration analysis of ras p21 products did not show any shift from the normal. Transplantation experiments demonstrated only 2 out of the 15 lines to be tumorigenic in nude mice. When 4 of the non-tumorigenic MLEC lines were transfected with cloned activated c-H-ras containing a point mutation within codon 61, they all became tumorigenic, the resultant neoplasms being hepatocellular carcinomas often associated with albumin mRNA expression. Our results thus indicate that ras activation is not necessary for immortalization or even for transformation of mouse liver cells in culture, and that ras activation may be an event during the progression process in mouse hepatocarcinogenesis in vivo.
Lee
G H
GH
Department of Pathology, Cancer Institute, Tokyo, Japan.
Sakai
R
R
Nagao
M
M
Kitagawa
T
T
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003062:Codon / Q000235:genetics; D015870:Gene Expression; D011905:Genes, ras / Q000502:physiology*; D008099:Liver / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D015689:Oncogene Protein p21(ras) / Q000032:analysis; D016133:Polymerase Chain Reaction; D014162:Transfection
D003062:Codon; D015689:Oncogene Protein p21(ras)