Transfection of cells with transforming growth factor-alpha leads to cellular resistance to the antiproliferative effects of tumor necrosis factor.

Journal Article

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)-alpha gene induces resistance to TNF. Colon carcinoma cell lines that express elevated levels of TGF-alpha 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-alpha 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.

Full Text

Duke Authors

Cited Authors

  • Aggarwal, BB; Pocsik, E; Ali-Osman, F; Totpal, K

Published Date

  • October 31, 1994

Published In

Volume / Issue

  • 354 / 1

Start / End Page

  • 12 - 16

PubMed ID

  • 7957892

International Standard Serial Number (ISSN)

  • 0014-5793

Language

  • eng

Conference Location

  • England