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Transfection of cells with transforming growth factor ‐α leads to cellular resistance to the antiproliferative effects of tumor necrosis factor
Author(s) -
Aggarwal Bharat B.,
Pocsik Eva,
Ali-Osman Francis,
Totpal Klara
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)01073-0
Subject(s) - tumor necrosis factor alpha , transfection , transforming growth factor , cytokine , biology , growth factor , cell culture , cell growth , growth inhibition , microbiology and biotechnology , intracellular , cancer research , receptor , growth factor receptor inhibitor , immunology , biochemistry , genetics
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.