Abstract
The roles of p38 MAP kinases and ERK in UVB induced cox-2 gene expression were studied in a human keratinocyte cell line, HaCaT. UVB significantly increased cox-2 gene expression at both protein and mRNA levels. As we reported previously, p38 and ERK were significantly activated after UVB irradiation in HaCaT cells. In addition, treating the cells with p38 inhibitor SB202190 or MEK inhibitor PD98059 specifically inhibited UVB induced p38 or ERK activation, respectively. In this study, we further examined the roles of p38 and ERK in UVB induced cox-2 gene expression in HaCaT cells. We found that SB202190 strongly inhibited UVB induced COX-2 protein expression at different time points and various UVB doses. Furthermore, SB202190 markedly inhibited UVB induced cox-2 mRNA. Our data indicated that ERK did not play a role in UVB induced cox-2 gene expression in human keratinocytes since suppression of ERK did not significantly alter UVB induced increase of COX-2 protein and mRNA. These results suggested, for the first time, that activation of p38 is required for UVB induced cox-2 gene expression in human keratinocytes. Since cox-2 expression plays an important role in UV carcinogenesis, p38 could be a potential molecular target for chemoprevention of skin cancer.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Allport VC, Slater DM, Newton R, Bennett PR . 2000 Mol. Hum. Reprod. 6: 561–565
Ananthaswamy HN, Pierceall WE . 1990 Photochem. Photobiol. 52: 1119–1136
Arbabi S, Rosengart MR, Garcia I, Maier RV . 2000 Surgery 128: 198–205
Barthelman M, Chen W, Gensler HL, Huang C, Dong Z, Bowden GT . 1998 Cancer Res. 58: 711–716
Bennett A, Carroll MA, Stamford IF, Whimster WF, Williams F . 1982 Br. J. Cancer 46: 888–893
Borsch-Haubold AG, Pasquet S, Watson SP . 1998 J. Biol. Chem. 273: 28766–28772
Buckman SY, Gresham A, Hale P, Hruza G, Anast J, Masferrer J, Pentland AP . 1998 Carcinogenesis 19: 723–729
Chen W, Bowden GT . 1999 Oncogene 18: 7469–7476
Chen W, Bowden GT . 2000 Mol. Carcinog. 28: 196–202
Chen W, Barthelman M, Martinez J, Alberts D, Gensler HL . 1997 Nutr. Cancer 29: 205–211
Chen W, Borchers AH, Dong Z, Powell MB, Bowden GT . 1998 J. Biol. Chem. 273: 32176–32181
Chen W, Dong Z, Valcic S, Timmermann BN, Bowden GT . 1999 Mol. Carcinog. 24: 79–84
Chulada PC, Doyle C, Gaul B, Tiano H, Mahler J, Lee C, Morham S, Langenbach R . 1998 Proc. Am. Assoc. Cancer Res. 39: 195
Cobb MH . 1999 Prog. Biophys. Mol. Biol. 71: 479–500
Coso OA, Chiariello M, Kalinec G, Kyriakis JM, Woodgett J, Gutkind JS . 1995 J. Biol. Chem. 270: 5620–5624
de Gruijl FR, Forbes PD . 1995 Bioessays 17: 651–660
Dean JL, Brook M, Clark AR, Saklatvala J . 1999 J. Biol. Chem. 274: 264–269
DiGiovanni J . 1992 Pharmacol. Ther. 54: 63–128
Fischer SM, Lo HH, Gordon GB, Seibert K, Kelloff G, Lubet RA, Conti CJ . 1999 Mol. Carcinog. 25: 231–240
Furstenberger G, Marks F . 1990 Eicosanoids and the Skin. Ruzicka T. (ed.) CRC Press: Boca Raton, FL pp. 108–124
Geijsen N, Dijkers PF, Lammers JJ, Koenderman L, Coffer PJ . 2000 FEBS Lett. 471: 83–88
Gresham A, Masferrer J, Chen X, Leal-Khouri S, Pentland AP . 1996 Am. J. Physiol. 270: C1037–C1050
Grewe M, Trefzer U, Ballhorn A, Gyufko K, Henninger H, Krutmann J . 1993 J. Invest. Dermatol. 101: 528–531
Hall EJ, Astor M, Bedford J, Borek C, Curtis SB, Fry M, Geard C, Hei T, Mitchell J, Oleinick N, Rubin J, Tu A, Ullrich R, Waldren C, Ward J . 1988 Am. J. Clin. Oncol. 11: 220–252
Hazan-Halevy I, Seger R, Levy R . 2000 J. Biol. Chem. 275: 12416–12423
Higashi Y, Kanekura T, Kanzaki T . 2000 Int. J. Cancer 86: 667–671
Hiller G, Sundler R . 1999 Cell Signal. 11: 863–869
Huang C, Ma WY, Bowden GT, Dong Z . 1996 J. Biol. Chem. 271: 31262–312688
Kang-Rotondo CH, Miller CC, Morrison AR, Pentland AP . 1993 Am. J. Physiol. 264: C396–C401
Marks F, Furstenberger G . 2000 Eur. J. Cancer. 36: 314–329
Miller C, Zhang M, He Y, Zhao J, Pelletier JP, Martel-Pelletier J, Di Battista JA . 1998 J. Cell Biochem. 69: 392–413
Nemoto S, Xiang J, Huang S, Lin A . 1998 J. Biol. Chem. 273: 16415–16420
Pages G, Milanini J, Richard DE, Berra E, Gothie E, Vinals F, Pouyssegur J . 2000 Ann. NY. Acad. Sci. 902: 187–200
Parfenova H, Balabanova L, Leffler CW . 1998 Am. J. Physiol. 274: C72–C81
Pentland AP, Needleman P . 1986 J. Clin. Invest. 77: 246–251
Pentland AP, Schoggins JW, Scott GA, Khan KN, Han R . 1999 Carcinogenesis 20: 1939–1944
Rigas B, Goldman IS, Levine L . 1993 J. Lab. Clin. Med. 122: 518–523
Sheng H, Shao J, Morrow JD, Beauchamp RD, DuBois RN . 1998 Cancer Res. 58: 362–366
Smith WL, Garavito RM, De Witt DL . 1996 J. Biol. Chem. 271: 33157–33160
Thomson S, Mahadevan LC, Clayton AL . 1999 Semin. Cell Dev. Biol. 10: 205–214
Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN . 1998 Cell 93: 705–716
Vane JR, Bakhle YS, Botting RM . 1998 Annu. Rev. Pharmacol. Toxicol. 38: 97–120
Xie W, Herschman HR . 1995 J. Biol. Chem. 270: 27622–27628
Yang T, Huang Y, Heasley LE, Berl T, Schnermann JB, Briggs JP . 2000 J. Biol. Chem. 275: 23281–23286
Acknowledgements
We thank Ms Anne Cione for secretarial assistance. This work was supported in part by NIH grant CA27502, Cancer Center Core Grant CA23074, and Center for Toxicology Grant p30 ESO6694.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chen, W., Tang, Q., Gonzales, M. et al. Role of p38 MAP kinases and ERK in mediating ultraviolet-B induced cyclooxygenase-2 gene expression in human keratinocytes. Oncogene 20, 3921–3926 (2001). https://doi.org/10.1038/sj.onc.1204530
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1204530
Keywords
This article is cited by
-
Wild chrysanthemum extract prevents UVB radiation-induced acute cell death and photoaging
Cytotechnology (2016)
-
Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats
BMC Complementary and Alternative Medicine (2013)
-
cis-Urocanic Acid Enhances Prostaglandin E2 Release and Apoptotic Cell Death via Reactive Oxygen Species in Human Keratinocytes
Journal of Investigative Dermatology (2011)
-
Ultraviolet B irradiation and activation of protein kinase D in primary mouse epidermal keratinocytes
Oncogene (2011)
-
Cyclooxygenase-dependent signaling is causally linked to non-melanoma skin carcinogenesis: pharmacological, genetic, and clinical evidence
Cancer and Metastasis Reviews (2011)