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Role of activated c‐H‐ras Oncogene in the induction and progression of immortal liver epithelial cell lines derived from normal C3H mice
Author(s) -
Lee GangHong,
Sakai Ryuichi,
Nagao Minako,
Kitagawa Tomoyuki
Publication year - 1991
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910470112
Subject(s) - transfection , microbiology and biotechnology , point mutation , biology , oncogene , cell culture , 3t3 cells , mutation , malignant transformation , messenger rna , cancer research , cell , gene , cell cycle , genetics
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 p2l products did not show any shift from the normal. Transplantation experiments demonstrated only 2 out of the 15 lines to be tu‐morigenic 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 hepatocarcinogene‐sis in vivo .