Transfection of cells with transforming growth factor‐α leads to cellular resistance to the antiproliferative effects of tumor necrosis factor

FEBS Letters

Pocsik, Eva²  Ali-Osman, Francis¹  Aggarwal, Bharat B.²  Totpal, Klara² 

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

关键词: Transforming growth factor (TGF)-α;    TNF;    Kinase;    Receptor;    Cytokine resistance;    Glutathione;    Cell proliferation;    TNF;    tumor necrosis factor;    TGF-α;    transforming growth factor;    INF;    interferon;    EGF;    epidermal growth factor;    FBS fetal bovine serum;    GSH;    glutathione;   

DOI  :  10.1016/0014-5793(94)01073-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Tumor necrosis factor (TNF) is a growth-modulatory cytokine that inhibits the growth of certain cell lines, stimulates the growth of some, and has no effect on the growth of still others. The molecular basis for this differential regulation of growth by TNF is not understood. We postulate that the growth of normal or tumor cells is determined by the balance between growth-stimulatory and -inhibitory signals. In the present study, we demonstrate that the transfection of cells with the transforming growth factor (TGF)-α gene induces resistance to TNF. Colon carcinoma cell lines that express elevated levels of TGF-α were also found to be resistant to this cytokine. Exogenous addition of the growth factor was also effective in decreasing the antiproliferative effects of TNF. Transfection of cells with the TGF-α gene led to downmodulation of TNF receptors but an increase in intracellular glutathione levels. Thus, these results support our hypothesis that expression of growth factors by certain tumor cells can lead to resistance to antiproliferative agents such as TNF.

【 授权许可】

Unknown