Expression of transforming growth factor-alpha mRNA in livers of patients with chronic viral hepatitis and hepatocellular carcinoma

BACKGROUND. Transforming growth factor-alpha (TGF alpha) is an important au tocrine growth factor of hepatocytes. The authors evaluated the roles of TG F alpha in chronic viral hepatitis (CVH) and hepatocellular carcinoma (HCC) . METHODS, The authors measured the amounts of TGF alpha mRNA in liver tissue s from 18 patients with HCC, 31 patients with CVH, and 7 normal controls. " Hot-start" reverse transcription-polymerase chain reaction (RT-PCR) using o ligo-dT and specific primers detected TGF alpha mRNA in total cellular RNA extracted from liver tissues. The levels of TGF alpha mRNA were determined by the end point titers of serial, two-fold dilutions of cDNA. The amounts of hepatitis B virus RNA (HBV-RNA) in livers of patients with chronic hepat itis B also were measured by Northern blot hybridization. RESULTS. TGFa mRNA levels were extremely higher in patients with HCC compar ed with patients with CVH and normal controls, and the levels in patients w ith CVH also were elevated compared with normal controls. The levels of TGF alpha mRNA were overexpressed in the underlying livers of patients with HC C compared with patients with CVH, although they were lower than those foun d in HCC tissues. The levels of TGF alpha mRNA were higher in samples from patients with chronic hepatitis B than in samples from patients with chroni c hepatitis C. The levels of TGF alpha mRNA were not correlated with serum alanine aminotransferase or HBV-RNA levels in liver tissues in patients wit h chronic hepatitis B. However, the expression of TGF alpha mRNA tended to be higher in the livers of patients with raised serum a-fetoprotein levels. CONCLUSIONS. The overexpression of TGF alpha mRNA in the liver seems to be associated with the regeneration of hepatocytes rather than hepatic necrosi s or viral replication. Also, it may be related closely to the development or progression of HCC, especially in the livers of patients with chronic he patitis B. (C) 2000 American Cancer Society.