Expression of insulin receptor substrate-1 in hepatocytes: an investigation using monoclonal antibodies

• Published in: Cancer letters Vol. 84; no. 1; p. 85
• Main Authors: Furusaka, A, Nishiyama, M, Ohkawa, K, Yamori, T, Tsuruo, T, Yonezawa, K, Kasuga, M, Hayashi, S, Tanaka, T
• Format: Journal Article
• Language: English
• Published: Ireland 29-08-1994
• Subjects: Animals; Antibodies, Monoclonal - biosynthesis; Carcinoma, Hepatocellular - etiology; CHO Cells; Cricetinae; Humans; Immunohistochemistry; Insulin Receptor Substrate Proteins; Liver - chemistry; Liver - cytology; Liver Cirrhosis, Experimental - metabolism; Liver Neoplasms, Experimental - etiology; Mice; Mice, Inbred BALB C; Phosphoproteins - analysis; Sensitivity and Specificity; Subcellular Fractions - chemistry
• ISSN: 0304-3835
• DOI: 10.1016/0304-3835(94)90361-1

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.