Miyoshi E, Higashiyama S, Nakagawa T, Suzuki K, Horimoto M, Hayashi N, Fusamoto H, Kamada T, Taniguchi N
Department of Biochemistry, Osaka University Medical School, Japan.
Int J Cancer. 1996 Oct 9;68(2):215-8. doi: 10.1002/(SICI)1097-0215(19961009)68:2<215::AID-IJC13>3.0.CO;2-9.
Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a member of the EGF family and is highly expressed in hepatoma tissues but not in normal liver. However, it is unknown when HB-EGF is induced during hepatocarcinogenesis and what are the mechanisms underlying its high expression in hepatoma. To address this issue, the expression of HB-EGF was investigated during hepatocarcinogenesis in LEC (Long-Evans with a cinnamon-like coat color) rats, which spontaneously develop hepatitis and hepatoma. LEA (Long-Evans with an agouti coat color) rats were used as controls. Furthermore, the induction of HB-EGF mRNA by various agents was investigated in a rat hepatoma cell line and hepatocytes in primary culture. Expression of HB-EGF mRNA in the liver was very low at the stage of acute and chronic hepatitis and markedly increased at the stage of hepatoma in LEC rats. Non-involved tissues adjacent to hepatoma showed low expression of HB-EGF mRNA. Immunochemical studies revealed positive staining in hepatoma tissues. Induction of HB-EGF mRNA by several growth factors was observed in a hepatoma cell line but not in normal hepatocytes. Our results suggest that HB-EGF is associated with the early progression steps of hepatoma.
肝素结合表皮生长因子（EGF）样生长因子（HB-EGF）是表皮生长因子家族的一员，在肝癌组织中高表达，而在正常肝脏中不表达。然而，HB-EGF在肝癌发生过程中何时被诱导以及其在肝癌中高表达的机制尚不清楚。为了解决这个问题，我们研究了LEC（具有肉桂色被毛的Long-Evans大鼠）大鼠肝癌发生过程中HB-EGF的表达，LEC大鼠会自发发生肝炎和肝癌。LEA（具有刺豚鼠色被毛的Long-Evans大鼠）用作对照。此外，还在大鼠肝癌细胞系和原代培养的肝细胞中研究了各种因子对HB-EGF mRNA的诱导作用。在LEC大鼠中，急性和慢性肝炎阶段肝脏中HB-EGF mRNA的表达非常低，而在肝癌阶段则明显增加。肝癌旁未受累组织中HB-EGF mRNA的表达较低。免疫化学研究显示肝癌组织中有阳性染色。在肝癌细胞系中观察到几种生长因子对HB-EGF mRNA的诱导作用，而在正常肝细胞中未观察到。我们的结果表明，HB-EGF与肝癌的早期进展步骤有关。
