pp60ν‐srckinase overexpression leads to cellular resistance to the antiproliferative effects of tumor necrosis factor

FEBS Letters

Budde, Raymond J.A.²  Pocsik, Eva³  Ali-Osman, Francis¹  Aggarwal, Bharat B.³  Totpal, Klara³ 

[1] Cytokine Research Laboratory, Departments of Experimental Pediatrics The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA;Cytokine Research Laboratory, Departments of Neuro-Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA;Cytokine Research Laboratory, Departments of Clinical Immunology and Biological Therapy, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA

关键词: pp60v-src;    TNF;    Kinase;    Cytokine;    Resistance;    Oncogene;    Proliferation;    TNF;    tumor necrosis factor;    IFN;    interferon;    IL;    interleukin;    EGF;    epidermal growth factor;    bFGF;    basic fibroblast growth factor;    FBS;    fetal bovine serum;    GSH;    glutathione;   

DOI  :  10.1016/0014-5793(94)00441-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 pp60 ^v-src oncogene.

【 授权许可】

Unknown