Roles of EGFR-Stat3 signal pathway in carcinogenesis of experimental hepatoma in rats

• Published in: Journal of cancer research and clinical oncology 2007-03, Vol.133 (3), p.145-152
• Main Authors: Yu, Xiao Tang, Zhu, Shi Neng, Xu, Zu De, Hu, Xi Qi, Zhu, Teng Fang, Chen, Jie Qing, Lu, Shi Lun
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Apoptosis; Biological and medical sciences; Carcinogens; Carcinoma, Hepatocellular - chemically induced; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - physiopathology; Cell Cycle; Cell Transformation, Neoplastic - metabolism; Disease Models, Animal; Gastroenterology. Liver. Pancreas. Abdomen; Genetics; Hepatology; Hybridization; Immunohistochemistry; Immunology; In Situ Hybridization; Liver Cirrhosis - metabolism; Liver Neoplasms, Experimental - chemically induced; Liver Neoplasms, Experimental - metabolism; Liver Neoplasms, Experimental - pathology; Liver Neoplasms, Experimental - physiopathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Models, Biological; p-Dimethylaminoazobenzene - analogs & derivatives; Pharmacology. Drug treatments; Phosphorylation; Proliferating Cell Nuclear Antigen - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Rats, Wistar; Receptor, Epidermal Growth Factor - metabolism; RNA, Messenger - genetics; Rodents; Signal Transduction; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Transforming Growth Factor alpha - metabolism; Tumors
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-006-0139-z

The purpose of this study is to investigate if the EGFR-Stat3 signal pathway contributes to the carcinogenesis of hepatoma in rats. Hepatoma was induced in rats by 3'Me-DAB as a model. EGFR, TGFalpha, Stat3, p-Stat3 in different stages of carcinogenesis were detected by immunohistochemistry and Western blot. In situ hybridization was applied to investigate the expression of Stat3 mRNA. The expressions of signal molecules were assessed by KS400 Image Analysis system. The data were statistically evaluated. EGFR, TGFalpha, Stat3 were highly expressed in the stages of liver necrosis and repairment. All hepatocellular carcinoma cases revealed elevated expression of EGFR, TGFalpha. Elevation of Stat3 mRNA and protein levels were identified, increase of activation of Stat3 was also observed. In HCC, there was positive correlation between p-Stat3 level and the expression of TGFalpha and PCNA. Increased expression of Bcl-2 (P < 0.05) coincided with elevated level of p-Stat3. Therefore, the EGFR-Stat3 signal pathway was related to the development of hepatoma in rats. TGFalpha-EGFR autocrine ring formation may lead to the activation of Stat3 and in turn, promote proliferation and regulate the transcription of genes regulating cell apoptosis and cell cycle.