Suppression of antiproliferative effects of tumor necrosis factor by transfection of cells with human platelet-derived growth factor B/c-sis gene.
The growth of cells is determined by the balance between growth-stimulatory and growth-inhibitory signals. In the present study, we demonstrate that the transfection of NIH 3T3 cells with a platelet-derived growth factor (PDGF-Blc-sis) gene induces resistance to the anticellular effects of tumor necrosis factor (TNF). Human tumor cell lines that express elevated levels of c-sis (e.g. epidermoid carcinoma, A-431) are also TNF resistant, whereas those that express no significant levels of this gene (e.g. breast adenocarcinoma, MCF-7) are TNF sensitive. Transfection of cells with the c-sis gene leads to down-modulation of TNF receptors and also a decrease in intracellular glutathione levels. Thus, our results demonstrate that over-expression of PDGF-Blc-sis by certain tumor cells can lead to their protection from the anticellular effects of TNF.
Aggarwal
B B
BB
Department of Clinical Immunology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Pocsik
E
E
Totpal
K
K
Ali-Osman
F
F
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D005978:Glutathione