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Control of cell cycle progression in human mesothelioma cells treated with gamma interferon

Oncogene volume 20, pages 1085–1093 (2001)Cite this article

Abstract

Recombinant human interferon gamma (r-hu-IFNγ) exerts both antitumoral activity in the early stages of human malignant mesothelioma and a cytostatic effect in human mesothelioma (HM) cell lines in vitro. The antiproliferative effect of interferons (IFNs) reported in a variety of cells has been attributed to several mechanisms. In order to progress in the understanding of HM cell growth modulation by r-hu-IFNγ, modifications of cell cycle progression and expression of key cell cycle regulator proteins in response to r-hu-IFNγ were examined. Nine HM cell lines were studied, including one resistant to the antiproliferative effect of r-hu-IFNγ. Except in the resistant cell line r-hu-IFNγ produced an arrest in the G1 and G2-M phases of the cell cycle, associated with a reduction in both cyclin A and cyclin dependent kinase inhibitors (CDKIs) expression. Moreover cyclin B1/cdc2 activity was decreased. The present study provides the first evidence of a G2-arrest in r-hu-IFNγ-treated HM cell lines and indicates that HM cell lines, despite their tumorigenic origin still support cell cycle control. The cell cycle arrest induced by r-hu-IFNγ seems to depend on cyclin regulation through p21WAF1/CIP1- and p27Kip1-independent mechanisms and is not directly related to the induced DNA damage.

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References

  • Astoul P, Picat-Joosen D, Viallat JR and Boutin C. . 1998 Cancer 83: 2099–2104.

  • Bader T and Wietzerbin J. . 1994 Proc. Natl. Acad. Sci. USA 91: 11831–11835.

  • Bielefeldt-Ohmann H, Fitzpatrick DR, Marzo AL, Jarnicki AG, Musk AW and Robinson BWS. . 1995a J. Interferon Cytokine Res. 15: 213–223.

  • Bielefeldt-Ohmann H, Marzo AL, Himbeck RP, Jarnicki AG, Robinson BWS and Fitzpatrick DR. . 1995b Cancer Immunol Immunother. 40: 241–250.

  • Boehm U, Klamp T, Groot M and Howard JC. . 1997 Annu. Rev. Immunol. 15: 749–795.

  • Boutin C, Nussbaum E, Monnet I, Bignon J, Vanderschueren R, Guerin JC, Menard O, Mignot P, Dabouis G and Douillard JY. . 1994 Cancer 74: 2460–2467.

  • Bowman RV, Manning LS, Davis MR and Robinson BWS. . 1991 Cancer Chem. Pharmacol. 28: 420–426.

  • Bromberg J, Horvath CM, Wen Z, Schreiber RD and Darnell JE. . 1996 Proc. Natl Acad. Sci. USA 93: 7673–7678.

  • Buard A, Vivo C, Monnet I, Boutin C, Pilatte Y and Jaurand MC. . 1998 Cancer Res. 58: 840–847.

  • Chin YE, Kitawaga M, Su WC, You ZH, Iwamoto Y and Fu XY. . 1996 Science 272: 719–722.

  • Christmas TI, Manning LS, Garlepp MJ, Musk AW and Robinson BWS. . 1993 J. Interferon Res. 13: 9–12.

  • Cordon-Cardo C. . 1995 Am. J. Pathol. 147: 545–560.

  • Darzynkiewicz Z, Gong J, Juan G, Ardelt B and Traganos F. . 1996 Cytometry 25: 1–13.

  • de Toledo SM, Azzam EI, Keng P, Laffrenier S and Little JB. . 1998 Cell Growth Diff. 9: 887–896.

  • El-Deiry WS, Harper W, O'Connor PM, Velculescu VE, Canman CE, Jackman J, Pietenpol JA, Burrell M, Hill DE, Wang Y, Wiman KG, Mercer WE, Kastan MB, Kohn KW, Elledge SJ, Kinzler KW and Vogelstein B. . 1994 Cancer Res. 54: 1169–1174.

  • Fitzpatrick DR, Peroni DJ and Bielefeldt-Ohmann H. . 1995 Am. J. Respir. Cell. Mol. Biol. 12: 455–460.

  • Gooch JL, Herrera RE and Yee D. . 2000 Cell Growth Differ. 11: 335–342.

  • Grandér D, Sangfelt O and Erickson S. . 1997 Eur. J. Haematol. 59: 129–135.

  • Guo N, Faller DV and Vaziri C. . 2000 J. Biol. Chem. 275: 1715–1722.

  • Grousson J, Ffrench M, Concha M, Schmitt D and Peguet-Navarro J. . 2000 J. Invest. Dermatol. 114: 581–586.

  • Harvat BL and Jetten AM. . 1996 Cell Growth Diff. 7: 289–300.

  • Harvat BL, Seth P and Jetten AM. . 1997 Oncogene 14: 2111–2122.

  • Herzinger T, Funk JO, Hillmer K, Eick D, Wolf DA and Kind P. . 1995 Oncogene 11: 2151–2156.

  • Hobeika AC, Subramaniam PS and Johnson HM. . 1997 Oncogene 14: 1165–1170.

  • Jaiswal M, La Russo NF, Burgart LJ and Gores GJ. . 2000 Cancer Res. 60: 184–190.

  • Jaurand MC, Kheuang L, Magne L and Bignon J. . 1986 Mutat Res. 169: 141–148.

  • Kominsky S, Johnson HM, Bryan G, Tanabe T, Hobeika AC, Subramaniam PS and Torres B. . 1998 Oncogene 17: 2573–2579.

  • Kosaka C, Masuda J, Shimokado K, Zen K, Yokota T, Sasaguri T and Ogata J. . 1992 Atherosclerosis 97: 75–87.

  • Lazutka JR. . 1996 Mutat Res. 361: 95–105.

  • Liu N, Lucibello FC, Engeland K and Müller R. . 1998 Oncogene 16: 2957–2963.

  • Liu N, Lucibello FC, Körner K, Wolfraim LA, Zwicker J and Müller R. . 1997 Nuc. Acids Res. 25: 4915–4920.

  • Mandal M, Bandyopadhyay D, Goepfert TM and Kamar R. . 1998 Oncogene 16: 217–25.

  • Martin DM, Carlson RO and Feldman EL. . 1993 J. Neurosci. Res. 34: 489–501.

  • Monti G, Jaurand MC, Monnet I, Chrétien P, Saint-Etienne L, Zeng L, Portier A, Devillier P, Galanaud P, Bignon J and Emilie D. . 1994 Cancer Res. 54: 4419–4423.

  • Moro A, Calixto A, Suarez E, Araña MJ and Perea SE. . 1998 Biochem. Biophys. Res. Comm. 245: 752–756.

  • Ozaki Y, Edelstein MP and Duch DS. . 1988 Proc. Natl. Acad. Sci. USA 85: 1242–1246.

  • Peto J, Decarli A, La Vecchia C, Levi F and Negri E. . 1999 Br. J. Cancer 79: 667–672.

  • Phan-Bich L, Buard A, Petit JF, Zeng L, Tenu JP, Chrétien P, Monnet I, Boutin C, Bignon J, Lemaire G and Jaurand MC. . 1997 Am. J. Respir. Cell. Mol. Biol. 16: 178–186.

  • Sharma B and Iozzo RV. . 1998 J. Biol. Chem. 273: 4642–4646.

  • Sibinga NES, Wang H, Perrella MA, Endege WO, Patterson C, Yoshizumi M, Haber E and Lee ME. . 1999 J. Biol. Chem. 274: 12139–12146.

  • Spitkovsky D, Schulze A, Boye B and Jansen-Dürr P. . 1997 Cell Growth Differ. 8: 699–710.

  • Subramaniam S, Mujtaba MG, Paddy MR and Johnson HM. . 1999 J. Biol. Chem. 274: 403–407.

  • Subramaniam PS and Johnson HM. . 1997 J. Interferon Cytokine Res. 17: 11–15.

  • Takikawa O, Kuroiwa T, Yamazaki F and Kido K. . 1988 J. Biol. Chem. 263: 42041–42048.

  • Tiefenbrun N, Melamed D, Levy N, Resnitzky D, Hoffmann I, Reed S and Kimchi A. . 1996 Mol. Cell. Biol. 16: 3934–3944.

  • Townsley FM and Ruderman JV. . 1998 Trends Cell Biol. 8: 239–244.

  • Ungar S, Van der Meeren A, Tammilehto L, Linnainmaa K, Mattson K and Gerwin B. . 1996 Br. J. Cancer 74: 1534–1540.

  • Urashima M, Teoh G, Chauhan D, Hoshi V, Ogata A, Treon SP, Schlossman RL and Anderson KC. . 1997 Blood 90: 279–289.

  • Wang JA, Fan S, Yuan RQ, Ma YX, Meng Q, Golderg ID and Rosen EM. . 1999 Int. J. Radiat. Biol. 75: 301–316.

  • Xu J, Kim S, Chen M, Rockow S, Yi SE, Wagner AJ, Hay N, Weichselbaum RR and Li W. . 1995 Blood 86: 2774–2778.

  • Yamada H, Ochi K, Nakada S, Nemoto T and Horiguchi-Yamada J. . 1994 Mol. Cell. Biochem. 136: 117–123.

  • Zeng L, Buard A, Monnet I, Boutin C, Fleury J, Saint-Etienne L, Brochard P, Bignon J and Jaurand MC. . 1993 Int. J. Cancer 55: 515–520.

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Acknowledgements

We gratefully thank Boehringer Ingelheim, France, for providing r-hu-IFNγ. We also thank Margaret Lefevre for her help checking the English language of this manuscript. This work was supported by INSERM funds and a grant from the Ligue Nationale contre le Cancer, Comité du Val d'Oise. C Vivo was a fellow of the Association pour la Recherche contre le Cancer.

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Authors and Affiliations

  1. INSERM E 99.09, Université Paris Val de Marne Paris XII (EA 2345), Faculté de Médecine, 8 rue du Général Sarrail, Créteil, 94010, Cedex, France

    C Vivo, F Lévy, Y Pilatte, J Fleury-Feith, P Chrétien, I Monnet, L Kheuang & M C Jaurand

  2. Service d'Histologie et Biologie Tumorale, Hôpital Tenon, rue de la Chine, Paris, 75020, France

    J Fleury-Feith

  3. Service d'Immuno-hématologie, Centre Hospitalier Intercommunal 40, rue de Verdun, Créteil, 94010, Cedex, France

    P Chrétien

  4. Service de Pneumologie, Centre Hospitalier Intercommunal 40, avenue de Verdun, Créteil, 94010, Cedex, France

    I Monnet

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  1. C Vivo
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Vivo, C., Lévy, F., Pilatte, Y. et al. Control of cell cycle progression in human mesothelioma cells treated with gamma interferon. Oncogene 20, 1085–1093 (2001). https://doi.org/10.1038/sj.onc.1204199

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