Effect of Tumor Necrosis Factor-${\alpha}$(TNF) on the Expression of Oncogenes in ME-180 Human Cervical Carcinoma Cells

종양괴사인자(TNF)가 ME-180 사람 경부 암종세포에서 종양 발생 유전자의 발현에 미치는 영향

  • Han, Hyung-Mee (Immunotoxicology Division, Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Kim, Hyung-Soo (Immunotoxicology Division, Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Sohn, Kyung-Hee (Immunotoxicology Division, Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Choi, Kyoung-Baek (Immunotoxicology Division, Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Chung, Seung-Tae (Immunotoxicology Division, Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Kim, Jin-Ho (Immunotoxicology Division, Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Lee, Byung-Moo (College of Pharmacy, SungKyunKwan University) ;
  • Kim, Joo-Il (Immunotoxicology Division, Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration)
  • 한형미 (식품의약품안전본부 독성부 면역독성과) ;
  • 김형수 (식품의약품안전본부 독성부 면역독성과) ;
  • 손경희 (식품의약품안전본부 독성부 면역독성과) ;
  • 최경백 (식품의약품안전본부 독성부 면역독성과) ;
  • 정승태 (식품의약품안전본부 독성부 면역독성과) ;
  • 김진호 (식품의약품안전본부 독성부 면역독성과) ;
  • 이병무 (성균관대학교 약학대학) ;
  • 김주일 (식품의약품안전본부 독성부 면역독성과)
  • Published : 1997.10.01

Abstract

Tumor necrosis factor-${alpha}$ (TNF) induced a cytotoxic response in ME-180 cervical carcinoma cells in vitro. This cytotoxic response was accompanied by a temporal series of mitogenic stimuli : increased c-fos, c-jun and jun-B expression. Depletion of protein kinase C (PKC) by exposure of ME-180 cells to 100ng/ml phorbol myristate acetate (PMA) for 24hours almost completely abolished TNF-mediated increase in these signals, indicating that a PKC-dependent pathway is involved in TNF-mediated increases in the expression of c-fos, c-jun and jun-B. Characteristics of TNF receptors after exposure to 100ng/ml PMA or 24hours were not altered, suggesting that diminished induction of these oncogenes by TNF after PMA treatment is not due to any changes at the receptor level. To examine whether a PKC-dependent pathway is involved in TNF-mediated cytotoxicity in ME-180 cells, cytotoxicity was measured after depletion of PKC. No apparent changes in cytototoxicity after PKC depletion suggest that a PKC-dependent pathway is not involved in TNF-mediated cytotoxicity. Furthermore, results from cytotoxicity tests after exposure to staurosporine (PKC inhibitor) did not show any changes in the TNF-mediated cytotoxicity, confirming that a PKC-dependent pathway is not involved in this process. These data indicate that 1) TNF induces expression of c-fos, c-jun and jun-B oncogenes via a PKC-dependent pathway and 2) PKC-dependent expression of these three oncogenes by TNF may not be involved in TNF-mediated cytotoxicity in ME-180 cells.

Keywords

References

  1. Ann. N. Y. Acad. Sci. v.587 Metabolic responses to cachectin/TNF. Tracey, K. J.;Cerami, A.
  2. Ann. N. Y. Acad. Sci. v.766 TNF-α is an effective therapeutic target for rheumatoid arthritis. Feldmann, M.;Brennan, F. M.;Elliott, M. J.;Willams, R. O.;Maini, R. N.
  3. Crit. Care. Med. v.21 Tumor necrosis factor in the pathogenesis of infectious diseases. Beutler, B;Grau, G. E.
  4. FEBS. Lett. v.340 Molecular mechanisms of tumor necrosis factor-induced cytotoxicity, What we do understand and what we do not. Beyaert, R.;Fiers, W.
  5. Biochem. Biophys. Res. Commun. v.214 Cooperative effects of tumor necrosis factor-α and 1,25-dihydroxyvitamin D3 on growth inhibition, differentiation, and c-mycreduction in human promyelocytic leukemia cell line HL-60. Katakami, Y.;Nakao, Y.;Katakami, N.;Koizumi, T.;Ogawa, R.;Yamada, H.;Takai, Y.;Fujita, T.
  6. Proc. Natl. Acad. Sci. USA v.84 Tumor necrosis factor inhibits MYC expression in HL-60 cells at the level of mRNA transcription. Kronke, M.;Schluter, C.;Pfizenmaier, K.
  7. Cancer Res. v.49 Immunoregulation and production of tumor necrosis factor-α by human thymocytes. Reem, G. H.;Duggan, A.;Schleuning, M.
  8. Biochem. J. v.290 Tumor necrosis factor-induced cytotoxicity is accompanied by intracellular mitogenic signals in ME-180 human cervical carcinoma cells. Manchester, K. M.;Heston, W. D. W.;Donner, D. B.
  9. Science v.230 Recombinant tumor necrosis factor-α : Effect on proliferation of normal and transformed cells in vitro. Sugarman, B. J.;Aggarwal, B. B.;Hass, P. E.;Figari, I. S.;Palladino, M. A. Jr.;Shepard, H. M.
  10. Nature v.337 Prolonged activation of jun and collagenase genes by tumor necrosis factor-α. Brenner, D. A.;O'Hara, M.;Angel, P.;Chojkier, M.;Karin, M.
  11. J. Biol. Chem. v.265 Positive and negative regulation of a tumor necrosis factor response in melanoma cells. Johnson, S. E.;Baglioni, C.
  12. Eur. J. Immunol. v.20 Synergy of tumor necrosis factor with protein kinase C activators on T cell activation. Munoz-Fernandez, M. A.;Pimentel-Muinos, F. X.;Alonso, M. A.;Campanero, M.;Sanchez-Madrid, F.;Silva, A.;Alonso, J. L.;Fresno, M.
  13. Mole. cell. Endocri. v.97 Involvement of protein kinase C and protein tyrosine kinase pathways in tumor necrosis factor-α-induced clustering of ovarian theca-in-terstitial cells. Zachow, R. J.;Terranova, P. F.
  14. Biochem. Biophys. Res. Commun. v.199 Vinblastine-dependent down-modulation of TNF receptors in human osteosarcoma cells is mediated by protein kinase C activity. Boscoboinik, D.;Galeotti, T.;Azzi, A.
  15. Biophys. Res. Commun. v.141 Rapid modulation of tumor necrosis factor membrane receptors by activators of protein kinase C. Scheurich, P.;Unglaub, R.;Maxeiner, B.;Thoma, B.;Zugmaier, G.;Pfizenmaier, K.
  16. Arch. Biochem. Biophys. v.300 Regulation of the TNF-α receptor in human osteosarcoma cells : role of microtubules and of protein kinase C. Galeotti, T.;Boscoboinik, D.;Azzi, A.
  17. J. Exp. Med. v.166 Downregulation of tumor necrosis factor(TNF) sensitivity via modulation of TNF binding capacity by protein kinase C activators. Unglaub, R.;Maxeiner, B.;Thoma, B.;Pfizenmaier, K.;Scheurich, P.
  18. J. Biol. Chem. v.263 Tumor necrosis factor receptors and cytocidal activity are down-regulated by activators of protein kinase C. Johnson, S. E.;Baglioni, C.
  19. J. Biol. Chem. v.262 Effect of phorbol esters on down-regulation and redistribution of cell sruface receptors for tumor necrosis factor-α. Aggarwal, B. B.;Eessalu, T. E.
  20. J. Immunol. v.142 IL-1 and TNF transmodulate epidermal growth factor receptors by a protein kinase C-independent mechanism. Bird, T. A.;Saklatvala, J.
  21. J. Biol. Chem. v.265 Protein kinase C-in-dependent activation of nuclear factor kB by tumor necrosis factor. Meichle, A.;Schutze, S.;Hensel, G.;Brunsing, D.;Kronke, M.