Correlation between Bcl-2 overexpression and H-ras mutation in naturally occurring hepatocellular proliferative lesions of the B6C3F1 mouse.
The correlation between the mutation at codon 61 of the H-ras gene and the expression of the Bcl-2 protein was investigated in naturally occurring hepatocellular proliferative lesions in B6C3F1 mice. Specimens of histologically diagnosed neoplastic or preneoplastic lesions of the liver, obtained from the control mice used for 2-year carcinogenicity studies, were examined by immunohistochemical techniques. All of 25 lesions confirmed to be hepatocellular carcinomas stained positive for the Bcl-2 protein. Three of 12 foci of cellular alterations, as well as 24 of 42 hepatocellular adenomas, stained weakly positive. Bcl-2 protein was expressed to a greater degree in hepatocellular carcinomas as opposed to adenomas and confirmed by Western blot analysis. Seven of 18 hepatocellular adenomas that stained positive for Bcl-2 and three of 16 hepatocellular adenomas that stained negative had a mutation at codon 61 of the H-ras gene. Overexpression of Bcl-2 protein is likely to enhance the malignant turnover of the neoplastic cells, following a mutation at codon 61 of the H-ras gene particularly. These findings suggest that Bcl-2 overexpression and the mutation at codon 61 of the H-ras gene may be critical factors in the development of naturally occurring hepatocellular tumors in B6C3F1 mice.
Biosafety Research Center, Foods, Drugs and Pesticides, Shioshinden, Fukude-cho, Iwata-gun, Shizuoka, Japan. mari@anpyo.or.jp
M
M
Iida
H
H
Iwata
H
H
Inoue
M
M
Enomoto
N
N
Horie
K
K
Takeishi
D000818:Animals; D002455:Cell Division; D011905:Genes, ras / Q000502:physiology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000209:etiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*
D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2