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
S
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Meeker
W A
WA
Wiener
J R
JR
Berchuck
A
A
Bast
R C
RC
Boyer
C M
CM
D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D016372:RNA, Antisense / Q000235:genetics* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics* / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology*
D007375:Interleukin-1; D016372:RNA, Antisense; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha