pp60c-src Activation in hepatocellular carcinoma of humans... : Hepatology (original) (raw)

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Masaki, Tsutomu1, 4; Okada, Masato2; Shiratori, Yasushi M.D., Ph.D.*, 1; Rengifo, William1; Matsumoto, Kozou3; Maeda, Shinn1; Kato, Naoya1; Kanai, Fumihiko1; Komatsu, Yutaka1; Nishioka, Mikio4; Omata, Masao1

1Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan

2Division of Protein Metabolism, Institute for Protein Research, Osaka University, Suita, Osaka, Japan

3Institute for Animal Experimentation of University of Tokushima School of Medicine, Kuramoto, Tokushima, Japan

4Third Department of Internal Medicine, Ikenobe Miki-cho, Kagawa, Japan

*Address reprint requests to: Second Department of Internal Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan. Fax: 81-3-3814-0021.

Received July 07, 1998; Accepted January 01, 1998; previously published online December 30, 2003

Abstract

For the related Src kinases, a close correlation exists between elevated tyrosine kinase activity and cell transformation. However, the involvement of pp60_c-src_ in hepatocellular carcinoma (HCC) remains obscure. The aim of this study was to evaluate whether pp60_c-src_ tyrosine kinase activity is elevated in HCC. We analyzed the kinase activity of pp60_c-src_ in normal liver tissue, chronic hepatitis liver tissue, and tumorous and adjacent nontumorous portions of HCC tissue from patients and Long-Evans cinnamon (LEC) rats that are known to develop liver cancer spontaneously. The kinase activity of pp60_c-src_ was rarely detected in the normal human liver tissue and chronic hepatitis liver tissue, but it was elevated in tumorous and nontumorous portions of HCC tissue. Furthermore, the kinase activity of pp60_c-src_ was significantly elevated in tumorous tissues compared with nontumorous tissues. The kinase activity of pp60_c-src_ was also higher in poorly differentiated HCC. In addition, the kinase activity of pp60_c-src_ increased proportionately with the development of HCC of LEC rats. Our results suggest that activation of the protooncogene product pp60_c-src_ may play an important role in the malignant transformation of hepatocytes in human and LEC rats, and that it may be closely related to the histopathological grading of human HCC.