Transfection of ovarian cancer cells with tumor necrosis factor-alpha (TNF-alpha) antisense mRNA abolishes the proliferative response to interleukin-1 (IL-1) but not TNF-alpha.
Recombinant interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) can induce endogenous TNF-alpha mRNA expression and stimulate proliferation of epithelial ovarian cancer cells. In a previous report, proliferation induced by either cytokine could be partially blocked by soluble TNF-alpha receptor or by neutralizing antibodies against TNF-alpha. In the present study, we have transfected the ovarian cancer cell line OVCA 432 with vectors that contain the TNF-alpha gene in the antisense or sense orientation. Antisense-transfected cells showed a 4.5- to 26-fold reduction in IL-1-induced TNF-alpha secretion. Similarly, the stimulation of [3H]thymidine incorporation by IL-1 but not by TNF-alpha was blocked by TNF-alpha antisense transfection. These results are consistent with a model in which the macrophage-derived cytokines IL-1 and TNF-alpha might stimulate endogenous production of TNF-alpha that in turn could stimulate proliferation of ovarian cancer cells by autocrine growth regulation.
Wu, S; Meeker, WA; Wiener, JR; Berchuck, A; Bast, RC; Boyer, CM
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