transforming-growth-factor-alpha and Biliary-Tract-Diseases

Pancreaticobiliary maljunction is associated frequently with gall-bladder carcinoma. Although increased turnover of the gall-bladder epithelium in patients with pancreaticobiliary maljunction is thought to predispose to carcinogenesis, there is little data to confirm this hypothesis. In addition, no previously published study has addressed the process underlying cell proliferation. In this study, cell kinetics were first evaluated using two methods, proliferating cell nuclear antigen (PCNA) immunohistochemical staining and argyrophilic nucleolar organizer region (AgNOR) staining. Second, immunohistochemistry was used to investigate the expression of transforming growth factor-alpha (TGF alpha), a potential regulator of cell proliferation in the gall-bladder. The gall-bladders of 11 patients with pancreaticobiliary maljunction were studied, and 11 gall-bladders removed from patients during other surgery were used as controls. The number of PCNA-positive cells and the number of AgNOR per nucleus were significantly greater in the gall-bladders of patients with pancreaticobiliary maljunction than in the control gall-bladders. The expression of TGF alpha was also significantly greater in the gallbladders of patients with pancreaticobiliary maljunction than in the control gall-bladders. In conclusion, these results suggest that the increased TGF alpha expression induced by pancreaticobiliary maljunction promotes proliferation of the gall-bladder epithelium, which may lead to carcinogenesis.

Topics: Adolescent; Adult; Aged; Biliary Tract Diseases; Cell Division; Child; Child, Preschool; Epithelium; Female; Gallbladder; Humans; Immunohistochemistry; Infant; Male; Middle Aged; Nucleolus Organizer Region; Pancreatic Diseases; Proliferating Cell Nuclear Antigen; Silver Staining; Transforming Growth Factor alpha

Transforming growth factor-alpha (TGF-alpha) is a cytokines related to cell proliferation and transformation. Immunoreactive TGF-alpha protein is expressed in regenerating hepatocytes and interlobular bile ducts as well as in hepatocellular carcinoma. Although TGF-alpha is thought to play an important role in the intrahepatic biliary tree, its role in cellular physiology is poorly understood. This study investigates the expression of TGF-alpha and its messenger RNA (mRNA) in various hepatobiliary diseases. The authors showed by immunohistochemistry that TGF-alpha and its receptor, epidermal growth factor receptor (EGFR), were expressed in interlobular bile ducts, proliferating bile ductules, and most hepatocytes in various hepatobiliary liver tissues. They also showed by Western blot analysis that TGF-alpha protein was present in hepatic bile samples obtained from patients with obstructive jaundice. In situ hybridization showed that TGF-alpha mRNA was localized in hepatocytes of some pathological liver tissues, but it was absent in biliary epithelial cells of the same tissues. These findings suggest that TGF-alpha protein is produced by hepatocytes, and hepatocyte stimulation occurred as autocrine growth regulation. The release of TGF-alpha into hepatic bile caused biliary proliferation and transformation through EGFR, present on the existing cell surface membrane of biliary epithelial cells.

Topics: Bile; Biliary Tract Diseases; ErbB Receptors; Humans; Immunoblotting; Immunohistochemistry; In Situ Hybridization; Liver; Liver Diseases; RNA, Messenger; Transforming Growth Factor alpha