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J Cancer Res Clin Oncol (2007) 133:145152 DOI 10.1007/s00432-006-0139-z
ORIGINAL PAPER
Roles of EGFR-Stat3 signal pathway in carcinogenesis of experimental hepatoma in rats
Xiao Tang Yu Shi Neng Zhu Zu De Xu Xi Qi Hu Teng Fang Zhu Jie Qing Chen Shi Lun Lu
Received: 12 December 2005 / Accepted: 7 June 2006 / Published online: 10 October 2006 Springer-Verlag 2006
Abstract 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[H11032]Me-DAB as a model. EGFR, TGF[afii9825], Stat3, p-Stat3 in diVerent 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, TGF[afii9825], Stat3 were highly expressed in the stages of liver necrosis and repairment. All hepatocellular carcinoma cases revealed elevated expression of EGFR, TGF[afii9825]. Elevation of Stat3 mRNA and protein levels were identiWed, increase of activation of Stat3 was also observed. In HCC, there was positive correlation between p-Stat3 level and the expression of TGF[afii9825] 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. TGF[afii9825]-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.
Keywords EGFR Stat3 Rat
Experimental hepatoma
Introduction
EGFR is a 170 kDa transmembrane glycoprotein. It belongs to receptor tyrosine kinases and is expressed in most epithelial tissues. Binding the ligands such as transforming growth factor [afii9825] (TGF[afii9825]) or epidermal growth factor (EGF), EGFR can form homo- or heterodimeric complex which leads to activation of its own tyrosine kinase via autophosphorylation. This, in turn, activates intracellular signaling cascades, including the ras/MAP kinase, phosphatidylinositol-3-kinase, and signal transducer and activator of transcription-3 (Stat3) signal transduction pathways (Jorissen et al. 2003).
In recent years, evidence has been accumulated for the overexpression of the receptor and/or ligands such as TGF[afii9825], as well as ligand-independent receptor activation, that occurred in many types of epithelial cancers including breast, pancreas, and liver carcinoma...