Abstract
The contribution of the short wavelength ultraviolet (UV) component of sunlight to the aetiology of skin cancer has been widely acknowledged, although its direct contribution to tumour initiation or progression is still poorly understood. The loss of normal cell cycle controls, particularly checkpoint controls, are a common feature of cancer. UV radiation causes both G1 and G2 phase checkpoint arrest in vitro cultured cells. In this study we have investigated the cell cycle responses to suberythemal doses of UV on skin. We have utilized short-term whole organ skin cultures, and multi parameter immunohistochemical and biochemical analysis to demonstrate that basal and suprabasal layer melanocytes and keratinocytes undergo a G2 phase cell cycle arrest for up to 48 h following irradiation. The arrest is associated with increased p16 expression but no apparent p53 involvement. This type of organ culture provides a very useful model system, combining the ease of in vitro manipulation with the ability to perform detailed molecular analysis in a normal tissue environment.
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References
Campbell C, Quinn AG, Angus B, Farr PM, Rees JL . 1993 Cancer Res. 53: 2697–2699
Castellano M, Parmiani G . 1999 Melanoma Res. 9: 421–432
Chakraborty A, Pawelek J . 1993 J. Cell. Physiol. 157: 344–350
Chakraborty AK, Funasaka Y, Slominski A, Bolognia J, Sodi S, Ichihashi M, Pawelek JM . 1999 Ann. N.Y. Acad. Sci. 885: 100–116
Cliby WA, Roberts CJ, Cimprich KA, Stringer CM, Lamb JR, Schreiber SL, Friend SH . 1998 EMBO J. 17: 159–169
Dickson MA, Hahn WC, Ino Y, Ronfard V, Wu JY, Weinberg RA, Louis DN, Li FP, Rheinwald JG . 2000 Mol. Cell. Biol. 20: 1436–1447
Elder DE . 1989 J. Invest. Dermatol. 92: 297S–303S
Freeman SE, Gange RW, Sutherland JC, Matzinger EA, Sutherland BM . 1987 J. Invest. Dermatol. 88: 430–433
Friedmann PS, Gilchrest BA . 1987 J. Cell. Physiol. 133: 88–94
Gabrielli BG, Clark JM, McCormack AK, Ellem KA . 1997a J. Biol. Chem. 272: 28607–28614
Gabrielli BG, Clark JM, McCormack AK, Ellem KA . 1997b Oncogene 15: 749–758
Gabrielli BG, De Souza CP, Tonks ID, Clark JM, Hayward NK, Ellem KA . 1996 J. Cell Sci. 109: 1081–1093
Gabrielli BG, Sarcevic B, Sinnamon J, Walker G, Castellano M, Wang XQ, Ellem KA . 1999 J. Biol. Chem. 274: 13961–13969
Haddad MM, Xu W, Schwahn DJ, Liao F, Medrano EE . 1999 Exp. Cell Res. 253: 561–572
Herzinger T, Funk JO, Hillmer K, Eick D, Wolf DA, Kind P . 1995 Oncogene 11: 2151–2156
Honigsmann H, Brenner W, Tanew A, Ortel B . 1987 J. Photochem. Photobiol. B 1: 33–43
Huang LC, Clarkin KC, Wahl GM . 1996 Proc. Natl. Acad. Sci. USA 93: 4827–4832
Im S, Moro O, Peng F, Medrano EE, Cornelius J, Babcock G, Nordlund JJ, Abdel-Malek ZA . 1998 Cancer Res. 58: 47–54
Iyengar B . 1994 Melanoma Res. 4: 293–295
Ley KD, Ellem KA . 1992 Carcinogenesis 13: 183–187
Libow LF, Scheide S, DeLeo VA . 1988 Pigment Cell Res. 1: 397–401
Lu X, Lane DP . 1993 Cell 75: 765–778
McLane JA, Pawelek JM . 1988 Biochemistry 27: 3743–3747
Medrano EE, Im S, Yang F, Abdel-Malek ZA . 1995 Cancer Res. 55: 4047–4052
Milligan A, Gabrielli BG, Clark JM, Hayward NK, Ellem KA . 1998 Mutat. Res. 422: 43–53
Pavey S, Conroy S, Russell T, Gabrielli B . 1999 Cancer Res. 59: 4185–4189
Petrocelli T, Poon R, Drucker DJ, Slingerland JM, Rosen CF . 1996 Oncogene 12: 1387–1396
Quevedo Jr WC . 1969 Am. Zool. 9: 531–540
Ruas M, Peters G . 1998 Biochim. Biophys. Acta 1378: F115–F177
Sarkaria JN, Busby EC, Tibbetts RS, Roos P, Taya Y, Karnitz LM, Abraham RT . 1999 Cancer Res. 59: 4375–4382
Shapiro GI, Edwards CD, Ewen ME, Rollins BJ . 1998 Mol. Cell. Biol. 18: 378–387
Soufir N, Moles JP, Vilmer C, Moch C, Verola O, Rivet J, Tesniere A, Dubertret L, Basset-Seguin N . 1999 Oncogene 18: 5477–5481
Tada A, Suzuki I, Im S, Davis MB, Cornelius J, Babcock G, Nordlund JJ, Abdel-Malek ZA . 1998 Cell Growth Differ. 9: 575–584
Tam SW, Shay JW, Pagano M . 1994 Cancer Res. 54: 5816–5820
Thody AJ, Graham A . 1998 Pigment Cell Res. 11: 265–274
Wang XQ, Gabrielli BG, Milligan A, Dickinson JL, Antalis TM, Ellem KA . 1996 Cancer Res. 56: 2510–2514
Watters D, Garrone B, Coomer J, Johnson WE, Brown G, Parsons P . 1998 Biochem. Pharmacol. 55: 1691–1699
Wikonkal NM, Brash DE . 1999 J. Investig. Dermatol. Symp. Proc. 4: 6–10
Zhan Q, Antinore MJ, Wang XW, Carrier F, Smith ML, Harris CC, Fornace Jr AJ . 1999 Oncogene 18: 2892–2900
Ziegler A, Jonason AS, Leffell DJ, Simon JA, Sharma HW, Kimmelman J, Remington L, Jacks T, Brash DE . 1994 Nature 372: 773–776
Acknowledgements
We would like to thank Dr Nicholas Hayward for his continued support and Drs Hayward and Nick Saunders for critical reading of the manuscript. This project was funded by the National Health and Medical Research Council of Australia. B Gabrielli was supported by an Australian Research Council Fellowship.
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Pavey, S., Russell, T. & Gabrielli, B. G2 phase cell cycle arrest in human skin following UV irradiation. Oncogene 20, 6103–6110 (2001). https://doi.org/10.1038/sj.onc.1204707
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DOI: https://doi.org/10.1038/sj.onc.1204707
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