In vitro progression-associated c-H-ras activation in neoplastic hepatocyte lines established from SV40-T antigen gene-harboring transgenic mice.
In order to investigate the molecular mechanisms of multistep hepatocarcinogenesis in SV40-T antigen gene-harboring transgenic mice, 9 hepatocellular carcinoma (HCC) lines and 10 "preneoplastic" hepatocyte lines were established from the animals and their biological and molecular changes during culture were investigated. Three of the 9 HCC lines showed progression during culture in terms of growth rate and growth capability in soft agar and in nude mice. This progression was associated with the appearance of activated c-H-ras oncogene. Including these 3 lines, H-ras activation was observed in a total of 7 of the 9 HCC lines (78%), whereas it was found only in 1 of 10 (10%) "preneoplastic" hepatocyte lines. These data thus indicate that H-ras activation may be an event occurring at a relatively late stage of hepatocarcinogenesis in this transgenic mouse system and that it may serve towards completion of the carcinogenic process together with the T-antigen.
Li
H
H
Department of Pathology, Cancer Institute, Tokyo.
Liu
J
J
Nomura
K
K
Lee
G H
GH
Hino
O
O
Ohtake
K
K
Aizawa
S
S
Kitagawa
T
T
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000032:analysis*; D011905:Genes, ras; D008099:Liver / Q000737:chemistry*; D008114:Liver Neoplasms, Experimental / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011230:Precancerous Conditions / Q000737:chemistry* / Q000235:genetics; D014407:Tumor Cells, Cultured
D000952:Antigens, Polyomavirus Transforming