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UVB-induced activation and internalization of keratinocyte growth factor receptor

Oncogene volume 22, pages 2422–2431 (2003)Cite this article

Abstract

Ultraviolet irradiation of mammalian cells induces several events that include activation of growth factor receptors and triggering of signal transduction pathway. Most of the UV responses are mediated by the production of reactive oxygen species (ROS) and can be blocked by antioxidants. In this study, we analysed the effect of UVB irradiation at physiologic doses and that of the pro-oxidant agent cumene hydroperoxide (CUH) on the activation of the receptor for keratinocyte growth factor (KGF), a key mediator of epithelial growth and differentiation. Exposure to both UVB (30–150 mJ/cm2) and CUH (200 μ M of NIH3T3 KGFR (KGF receptors) transfectants caused a rapid tyrosine phosphorylation and activation of KGFR similar to that induced by KGF, and internalization of the activated receptor. The KGFR expression appeared unmodified by the treatments. Ultrastructural observations of both UVB- and CUH-treated cells showed a normal morphology of the plasma membranes and intracellular organelles. The antioxidant N-acetylcysteine inhibited UVB-induced receptor phosphorylation. The generation of an intracellular oxidative stress was detected as a decrease of catalase activity and of vitamin E, and reduced glutathione levels, whereas superoxide dismutase activity was not significantly modified. A peroxidation of polyunsaturated fatty acids of cell membranes was observed after both treatments, associated with the intracellular oxidative stress. Similar biochemical events were observed on NIH3T3 untransfected control cells, suggesting that KGFR activation follows intracellular generation of ROS and is not associated with a scavenging effect. Taken together our results demonstrate that exposure to UVB and to oxidant stimuli induces a rapid intracellular production of ROS, which in turn are capable of triggering KGFR activation and internalization, similar to those induced by KGF.

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Abbreviations

KGF:

keratinocyte growth factor

CUH:

cumene hydroperoxide

NAC:

N-acetylcysteine

PDTC:

pyrrolidine dithiocarbamate

ROS:

reactive oxygen species

SOD:

superoxide dismutase

Cat:

catalase.

References

  • Bae YS, Kang SW, Seo MS, Baines IC, Tekle E, Chock PB and Rhee SG . (1997). J. Biol. Chem., 272, 217–221.

  • Capone A, Visco V, Belleudi F, Marchese C, Cardinali G, Bellocci M, Picardo M, Frati L and Torrisi MR (2000). Cell Growth Differ., 11, 607–614.

  • Claiborne A . (1985). Handbook of Methods for Oxygen Radical Research. Greenwald RA (ed). CRC: Boca Raton, FL, pp. 283–284.

    Google Scholar 

  • Coffer PJ, Burgering BMT, Peppelenbosch MP, Bos JL and Kruijer W . (1995). Oncogene, 11, 561–569.

  • de Gruijl FR . (2000). Methods Enzymol., 319, 359–366.

  • Dimon-Gadal S . (1998). J. Biol. Chem., 273, 22833–22284.

  • Finch PW, Murphy F, Cardinale I and Krueger JG . (1997) Am. J. Pathol., 151, 1619–1628.

  • Finch PW, Rubin JS, Miki T, Ron D and Aaronson SA . (1989) Science, 245, 752–755.

  • Fisher GJ, Wang ZQ, Datta S, Varani J, Kang S and Voorhees JJ . (1997). New Engl. J. Med., 337, 1419–1428.

  • Fuchs J and Packer L . (1990). Photodermatol. Photoimmunol. Photomed., 7, 920–925.

  • Glenn McGregor W . (1999). J. Invest. Dermatol., 4, 1–5.

  • Hadari YR, Gotoh N, Kouhara H, Lax I and Schlessinger J . (2001). Proc. Natl. Acad. Sci. USA, 98, 8578–8583.

  • Hines MD and Allen-Hoffman BL . (1996). J. Biol. Chem., 271, 6245–6251.

  • Huang RP and Adamson ED . (1995). Oncogene, 10, 467–475.

  • Huang RP, Wu JX, Fan Y and Adamson ED . (1996). J. Cell. Biol., 133, 211–220.

  • Kayanoki Y, Fujii J, Islam KN, Suzuki K, Kawata S, Matsuzawa Y and Taniguchi N . (1996) J. Biochem. (Tokyo), 119, 817–822.

  • LaRochelle WJ, Dirsch OR, Finch PW, Cheon HG, May M, Marchese C, Pierce JH and, Aaronson SA . (1995). J. Cell Biol., 129, 357–366.

  • Marchese C, Chedid M, Dirsch OR, Csaky KG, Santanelli F, Latini C, LaRochelle WJ, Torrisi MR and Aaronson SA . (1995). J. Exp. Med., 182, 1369–1376.

  • Marchese C, Mancini P, Belleudi F, Felici A, Gradini R, Sansolini T, Frati L and Torrisi MR . (1998). J. Cell Sci., 111, 3517–3527.

  • Marchese C, Rubin JS, Ron D, Faggioni A, Torrisi MR, Messina A, Frati L and Aaronson SA . (1990). J. Cell Physiol., 144, 326–333.

  • Marchese C, Sorice M, De Stefano C, Frati L and Torrisi MR . (1997). Cell Growth Differ., 8, 989–997.

  • Miki T, Bottaro DP, Fleming TP, Smith CL, Burgess WH, Chan AML and Aaronson SA . (1992). Proc. Natl. Acad. Sci. USA, 89, 246–250.

  • Miki T, Fleming TP, Bottaro DP, Rubin JS, Ron D and Aaronson SA . (1991). Science (Washington, DC), 251, 72–75.

  • Ohba M, Shibanuma M, Kuroky T and Nose K . (1994). J. Cell Biol., 126, 1079–1088.

  • O'Neil P, Davies S and Fielden EM . (1998). J. Biochem., 24, 41–46.

  • Peus D, Meves A, Vasa RA, Beyerle A, O'Brien T and Pittelkow MR . (1999) Free Rad. Biol. Med., 27, 1197–1202.

  • Peus D, Vasa RA, Meves A, Pott M, Beyerle A, Squillace K and Pittelkow M . (1998). J. Invest. Dermatol., 110, 966–971.

  • Picardo M, Grammatico P, Roccella F, Roccella M, Grandinetti M, Del Porto G and Passi S . (1996). J. Invest. Dermatol., 107, 322–326.

  • Piccoli G, Fiorani M, Biagiarelli L, Palma F, Potenza L, Amicucci A and Stocchi V . (1994). J. Chromatogr., 676, 239–246.

  • Rosette C and Karin M . (1996). Science (Washington, DC), 274, 1194–1197.

  • Rubin JS, Osada H, Finch PW, Taylor W, Rudikoff S and Aaronson SA . (1989). Proc. Natl. Acad. Sci. USA, 86, 802–806.

  • Sachsenmaier C, Radler-Pohl A, ZincK R, Nordheim A, Herrlich P and Rahmsdorf HJ . (1994). Cell, 78, 963–972.

  • Schwarz A, Bhardway R, Aragane Y, Mahnke K, Riemann H, Metze D, Luger TA and Schwarz T . (1995). J. Invest. Dermatol., 104, 922–927.

  • Shaoul E, Reich-Slotky R, Berman B and Ron D . (1995). Oncogene, 10, 357–366.

  • Sheikh MS, Antinore MJ, Huang Y and Fornace AJ . (1998). Oncogene, 17, 2555–2563.

  • Staiano-Coico L, Krueger GJ, Rubin JS, D'limi S, Vallat VP, Valentino L, Fahey T, Hawes A, Kingston G, Madden MR, Mathwich M, Gottlieb AB and Aaronson SA . (1993). J. Exp. Med., 178, 865–878.

  • Vessey DA, Lee KH and Boyer TD . (1995). J. Invest. Dermatol., 104, 355–358.

  • Werner S, Peters KG, Longaker MT, Fuller-Pace F, Banda MJ and Williams LT . (1992). Proc. Natl. Acad. Sci. USA, 89, 6896–6900.

  • Werner S, Smola HM, Xiang L, Longaker MT, Krieg T, Hofschneider PH and Williams LT . (1994). Science, 266, 819–822.

  • Wikonkal NM and Brash DE . (1999). J. Invest. Dermatol., 4, 6–10.

  • Zhou Y, Lee HST, Kooshesh F, Fujisawa H, Sauder DN and Kondo S . (1996). Exp. Dermatol., 5, 138–144.

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Acknowledgements

This work was partially supported by grants from MURST, from Associazione Italiana per la Ricerca sul Cancro (AIRC), from CNR (Target Project on ‘Biotechnology’) and Ministero della Sanità Italy.

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Author notes

  1. Contributed equally to this work.

Authors and Affiliations

  1. Dipartimento di Medicina Sperimentale e Patologia, Università di Roma ‘La Sapienza’, viale Regina Elena 324, Rome, 00161, Italy

    Cinzia Marchese, Francesca Belleudi, Simona Ceccarelli, Luigi Frati & Maria Rosaria Torrisi

  2. Istituto Dermatologico Santa Maria e San Gallicano. IRCCS, Rome, Italy

    Vittoria Maresca, Giorgia Cardinali, Marinella Bellocci, Maria Rosaria Torrisi & Mauro Picardo

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  1. Cinzia Marchese
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  2. Vittoria Maresca
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Correspondence to Cinzia Marchese.

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Marchese, C., Maresca, V., Cardinali, G. et al. UVB-induced activation and internalization of keratinocyte growth factor receptor. Oncogene 22, 2422–2431 (2003). https://doi.org/10.1038/sj.onc.1206301

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