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Reduced C‐terminal Src kinase (Csk) activities in hepatocellular carcinoma
Author(s) -
Masaki Tsutomu,
Okada Masato,
Tokuda Masaki,
Shiratori Yasushi,
Hatase Osamu,
Shirai Mutsunori,
Nishioka Mikio,
Omata Masao
Publication year - 1999
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510290239
Subject(s) - proto oncogene tyrosine protein kinase src , hepatocellular carcinoma , terminal (telecommunication) , tyrosine protein kinase csk , carcinoma , cancer research , kinase , medicine , oncology , biology , sh3 domain , microbiology and biotechnology , computer science , receptor , computer network
The proto‐oncogene product pp60 c‐src is the cellular homologue of the Rous sarcoma transforming gene, and it is a non–receptor‐linked and membrane‐associated tyrosine kinase. There is a close correlation between elevated pp60 c‐src activity and cell transformation. We have recently reported that pp60 c‐src was activated in hepatocellular carcinoma (HCC) of human and Long‐Evans cinnamon (LEC) rats. However, the mechanisms involved in this process remain unknown. C‐terminal Src kinase (Csk) is a novel cytoplasmic protein tyrosine kinase that inactivates the members of the Src family protein tyrosine kinase in vitro . We investigated the role of Csk in hepatocarcinogenesis by analyzing the location, amount of Csk, and its kinase activity levels in nontumorous cirrhotic and tumorous sections of HCC of patients and an animal model of LEC rats. Csk tyrosine kinase activity was significantly reduced in tumorous tissues compared with nontumorous sections of patients as well as LEC rats. A single immunoreactive band at 50 kd was detected with Csk antibody in normal liver (NL), chronic hepatitis (CH), and nontumorous cirrhotic (NTC) segments of HCC of patients and LEC rats. In human tumorous tissues, Western blot revealed a 53‐kd immunoreactive band, which was slightly larger than the usual 50‐kd band of Csk. These results suggest that the reduced activity of tyrosine kinase of Csk may play an important role in the malignant transformation of hepatocytes in human and LEC rat, and the appearance of 53‐kd Csk‐related protein may be closely involved in the progression of cirrhosis to HCC in humans, and that 50‐kd Csk may act as an antioncogene through the negative regulation of pp60 c‐src in the development of human HCC