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pp60 ν‐ src kinase overexpression leads to cellular resistance to the antiproliferative effects of tumor necrosis factor
Author(s) -
Aggarwal Bharat B.,
Totpal Klara,
Ali-Osman Francis,
Budde Raymond J.A.,
Pocsik Eva
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)00441-2
Subject(s) - tumor necrosis factor alpha , proto oncogene tyrosine protein kinase src , tyrosine kinase , transfection , cancer research , oncogene , receptor , kinase , cytokine , biology , intracellular , microbiology and biotechnology , signal transduction , cell culture , immunology , cell , biochemistry , cell cycle , genetics
While some tumor cells are sensitive to the antiproliferative effects of tumor necrosis factor (TNF), others are resistant. The molecular basis for cellular resistance to TNF is not completely understood. Previously we have shown that transfection of cells with an oncogene HER2/neu/erb B2 , a receptor tyrosine kinase, leads to resistance to the anticellular effects of TNF [(1988) Proc. Natl. Acad. Sci. USA 85, 5102‐5106]. In the present study, we demonstrate that the overexpression of another oncogenic tyrosine kinase, pp60 v‐src also induces resistance to TNF. In contrast to HER2 , however, pp60 v‐src transfection of cells did not lead to down‐modulation of TNF receptors but rather to decreased intracellular glutathione levels. The pp60 v‐src ‐induced cellular resistance to TNF could be abrogated by interferon‐γ. Thus, these results indicate that the resistance of certain tumors to TNF may also be due in part to the overexpression of pp 60 v‐src oncogene.