Expression of insulin receptor substrate-1 in hepatocytes: an investigation using monoclonal antibodies.
To investigate the expression and subcellular distribution of insulin receptor substrate-1 in hepatocytes, which are major targets of insulin along with muscle and adipose tissue, we obtained monoclonal antibodies by immunizing mice with a fusion protein consisting of the C-terminal portion of the human insulin receptor substrate-1 and glutathione-S-transferase. Two of the monoclonal antibodies (designated as 7B3 and 6G5) were found to be useful for immunohistochemical studies. Using 6G5 we demonstrate a high level of expression of insulin receptor substrate-1 in liver cirrhosis hepatocytes and variable expression in hepatocellular carcinoma cells. These results suggest that insulin receptor substrate-1 may play a role in liver regeneration during cirrhosis and that an insulin signaling cascade may be involved in hepatocarcinogenesis.
Furusaka
A
A
Department of Internal Medicine (Daisan Hospital), Tokyo, Japan.
Nishiyama
M
M
Ohkawa
K
K
Yamori
T
T
Tsuruo
T
T
Yonezawa
K
K
Kasuga
M
M
Hayashi
S
S
Tanaka
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D016466:CHO Cells; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D006224:Cricetinae; D006801:Humans; D007150:Immunohistochemistry; D055504:Insulin Receptor Substrate Proteins; D008099:Liver / Q000737:chemistry* / Q000166:cytology; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000209:etiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010750:Phosphoproteins / Q000032:analysis*; D012680:Sensitivity and Specificity; D013347:Subcellular Fractions / Q000737:chemistry
D000911:Antibodies, Monoclonal; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins