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Reduced C‐terminal Src kinase activity is correlated inversely with pp60 c‐src activity in colorectal carcinoma
Author(s) -
Cam William Rengifo,
Masaki Tsutomu,
Shiratori Yasushi,
Kato Naoya,
Ikenoue Tsuneo,
Okamoto Makoto,
Igarashi Koichi,
Sano Takaaki,
Omata Masao
Publication year - 2001
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20010701)92:1<61::aid-cncr1292>3.0.co;2-d
Subject(s) - proto oncogene tyrosine protein kinase src , tyrosine protein kinase csk , tyrosine kinase , cancer research , kinase , cyclin dependent kinase 4 , medicine , microbiology and biotechnology , cyclin dependent kinase 2 , protein kinase a , biology , sh3 domain , biochemistry , receptor
BACKGROUND Specific kinase activity of the proto‐oncogene product pp60 c‐src is reported to be elevated in patients with carcinoma of the colon, and a novel cytoplasmic protein‐tyrosine kinase, C‐terminal Src kinase (Csk), has been found to inactivate the members of the Src family protein‐tyrosine kinase. In this study, Csk activity and pp60 c‐src activity were examined in colorectal tumors as well as in colon carcinoma cell lines. METHODS Colorectal carcinoma tissue and adjacent nonneoplastic tissue from 24 patients, from 8 colon carcinoma cell lines, and from 1 normal colon cell line were used. The levels of pp60 c‐src and Csk in colorectal tissue and cell lines were analyzed by Western and/or Northern blot analysis, and their kinase activity levels were measured by in‐gel kinase assay. RESULTS In the samples from 24 patients with colorectal carcinoma, pp60 c‐src kinase activity and protein levels were increased by 7.8 ± 0.55 and 2.6 ± 0.13 times the control levels, respectively. Conversely, the Csk protein level and its kinase activity were reduced by 0.53 ± 0.08 and 0.53 ± 0.09 times the control levels, respectively. pp60 c‐src kinase activity was correlated inversely with Csk activity (correlation coefficient = −0.71; P < 0.0001). Of the cell lines, pp60 c‐src kinase activity and protein levels, respectively, were 7.4 ± 1.22 and 1.86 ± 0.28 times greater than normal control levels. Csk protein level and kinase activity, respectively, were 0.54 ± 0.13 and 0.52 ± 0.11 times less normal control levels and were correlated with mRNA amount. CONCLUSIONS Csk mRNA, protein, and its kinase activity were reduced in colorectal carcinoma and were correlated with pp60 c‐src kinase activity level. The reduced activity of Csk may be involved in the transformation of a subset of colorectal carcinoma. Cancer 2001;92:61–70. © 2001 American Cancer Society.