Abnormal Expression of Hepatic Transforming Growth Factor-beta1 at the Early Stage of Hepatocellular Carcinoma Formation

AIM: The study was aimed to investigate the dynamic alteration of hepatic transforming growth factor (TGF)-beta1 expression during the formation of hepatocellular carcinoma. METHODS: The animal model for hepatocarcinogenesis was made with male Sprague-Dawley (SD) rats induced with 0.05% of 2-fluorenylacetamide. Morphological changes in rat livers were examined by Hematoxylin and Eosin staining. Hepatic total RNA was extracted from rat livers and TGF-beta1 mRNA level was analyzed by nested RT-PCR. The levels of TGF-beta1 in liver and blood were quantitatively detected by ELISA. Simultaneously, hepatocyte distribution of TGF-beta1 was analyzed by immunohistochemistry. RESULTS: Our histopathological data confirmed the 2-fluorenylacetamide-induced malignant transformation of rat hepatocytes progressed from granule-like degeneration to atypical hyperplasia to hepatoma formation. The expression levels of rat hepatic total RNA, TGF-beta1 mRNA, and TGF-beta1 protein were significantly increased with the histopathological changes. They were significantly higher in cancerous group than those in any group of control, hepatocyte degeneration, and precancerous lesion (P < 0.05). An increasing trend of hepatic TGF-beta1 protein was in accordance with TGF-beta1 mRNA, especially in precancerous or cancerous tissues, and a closely positive relationship was found between the levels of hepatic and circulating TGF-beta1 protein. CONCLUSION: Our data support that TGF-beta1 participates in hepatocarcinogenesis, and its abnormal expression is associated with malignant transformation of hepatocytes.