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  • Title: Cytokine-induced modulation of tumor suppressor gene expression in ovarian cancer cells: up-regulation of p53 gene expression and induction of apoptosis by tumor necrosis factor-alpha.
    Author: Gotlieb WH, Watson JM, Rezai A, Johnson M, Martínez-Maza O, Berek JS.
    Journal: Am J Obstet Gynecol; 1994 Apr; 170(4):1121-8; discussion 1128-30. PubMed ID: 8166195.
    Abstract:
    OBJECTIVE: Our purpose was to determine the effect of tumor necrosis factor-alpha on anti-oncogene expression and to investigate the relationship between the up-regulation of the p53 tumor suppressor gene and tumor necrosis factor-alpha-mediated apoptosis in epithelial ovarian cancer cell lines. STUDY DESIGN: By means of Northern blot techniques p53 messenger ribonucleic acid expression was assayed in ovarian cancer cells. Tumor cells explanted from patients into Balb/c nude mice were exposed to supernatants from activated monocytes, activated T cells, or the recombinant cytokines interleukin-6 and tumor necrosis factor-alpha. Time- and dose-dependence of p53 up-regulation was measured. Induction of programmed cell death (apoptosis) by tumor necrosis factor-alpha was quantitated by means of a deoxyribonucleic acid fragmentation assay. RESULTS: Detectable levels of messenger ribonucleic acid for p53 were seen in ovarian cancer cells. Tumor necrosis factor-alpha induced a significant up-regulation of p53 messenger ribonucleic acid levels in ovarian cancer cells grown in nude mice and in vitro, whereas interleukin-6 did not. The maximum level of induction was 8 hours, and the up-regulation of p53 was dose dependent. In addition, tumor necrosis factor-alpha induced a dose-dependent increase in deoxyribonucleic acid fragmentation. CONCLUSION: Tumor necrosis factor-alpha induced up-regulation of p53 tumor suppressor gene expression in epithelial ovarian cancer cell lines, together with the induction of cell death by apoptosis.
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