title: Sunlight UV-induced skin cancer relies upon activation of the p38α signaling pathway.
abstract: The activation of cellular signal transduction pathways by solar ultraviolet (SUV) irradiation plays a vital role in skin tumorigenesis. Although many pathways have been studied using pure ultraviolet A (UVA) or ultraviolet B (UVB) irradiation, the signaling pathways induced by SUV (i.e., sunlight) are not understood well enough to permit improvements for prevention, prognosis, and treatment. Here, we report parallel protein kinase array studies aimed at determining the dominant signaling pathway involved in SUV irradiation. Our results indicated that the p38-related signal transduction pathway was dramatically affected by SUV irradiation. SUV (60 kJ UVA/m(2)/3.6 kJ UVB/m(2)) irradiation stimulates phosphorylation of p38α (MAPK14) by 5.78-fold, MSK2 (RPS6KA4) by 6.38-fold, and HSP27 (HSPB1) by 34.56-fold compared with untreated controls. By investigating the tumorigenic role of SUV-induced signal transduction in wild-type and p38 dominant-negative (p38 DN) mice, we found that p38 blockade yielded fewer and smaller tumors. These results establish that p38 signaling is critical for SUV-induced skin carcinogenesis.
authors: The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
authors: Kangdong
authors: K
authors: Liu
authors: Donghoon
authors: D
authors: Yu
authors: Yong-Yeon
authors: YY
authors: Cho
authors: Ann M
authors: AM
authors: Bode
authors: Weiya
authors: W
authors: Ma
authors: Ke
authors: K
authors: Yao
authors: Shengqing
authors: S
authors: Li
authors: Jixia
authors: J
authors: Li
authors: G Tim
authors: GT
authors: Bowden
authors: Ziming
authors: Z
authors: Dong
authors: Zigang
authors: Z
authors: Dong
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D002478:Cells, Cultured; D005799:Genes, Dominant; D006801:Humans; D051379:Mice; D008812:Mice, Hairless; D018345:Mice, Knockout; D010766:Phosphorylation / Q000528:radiation effects; D040081:Protein Array Analysis; D015398:Signal Transduction / Q000528:radiation effects*; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D013472:Sunlight / Q000009:adverse effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
chemical_list: D048051:p38 Mitogen-Activated Protein Kinases
references: Biochem Pharmacol. 2010 Dec 15;80(12):2042-9
references: 20599768
references: Cancer Res. 2008 May 15;68(10):3752-8
references: 18483258
references: Int J Oncol. 2001 Mar;18(3):461-6
references: 11179472
references: Mol Cell Biochem. 2000 Sep;212(1-2):19-28
references: 11108132
references: Carcinogenesis. 2009 Feb;30(2):321-30
references: 19073879
references: Mol Carcinog. 2011 Jun;50(6):469-78
references: 21268131
references: Mol Cancer Ther. 2007 Jan;6(1):299-308
references: 17218637
references: Mol Cell Biol. 2009 Apr;29(8):2168-80
references: 19204086
references: J Cutan Pathol. 2009 Jul;36(7):760-5
references: 19519607
references: J Clin Invest. 2007 Dec;117(12):3658-60
references: 18060027
references: Exp Dermatol. 2010 Aug;19(8):e222-7
references: 20557351
references: J Biol Chem. 2002 Oct 25;277(43):40944-9
references: 12189144
references: J Cell Physiol. 2012 Mar;227(3):1168-78
references: 21604264
references: Mol Cell Biol. 2000 Feb;20(4):1436-47
references: 10648628
references: Carcinogenesis. 2007 Jul;28(7):1543-51
references: 17404396
references: Carcinogenesis. 2004 May;25(5):713-22
references: 14729583
references: Br J Dermatol. 2005 Jan;152(1):43-51
references: 15656799
references: Adv Exp Med Biol. 2008;624:117-24
references: 18348452
references: Exp Cell Res. 2005 Aug 15;308(2):459-68
references: 15950217
references: Cell. 2007 Jan 26;128(2):295-308
references: 17254968
references: Cancer Lett. 2008 Jun 8;264(1):127-34
references: 18442668
references: Curr Cancer Drug Targets. 2007 Jun;7(4):325-34
references: 17979627
references: FEBS Lett. 2009 Jul 7;583(13):2208-12
references: 19527717
references: Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13716-21
references: 21844338
references: Photochem Photobiol. 2001 Aug;74(2):274-82
references: 11547566
references: J Biol Chem. 2011 Aug 26;286(34):29601-9
references: 21715333
references: Oncogene. 2001 Jun 28;20(29):3921-6
references: 11439356
references: J Photochem Photobiol B. 2001 Oct;63(1-3):19-27
references: 11684448
references: Photochem Photobiol. 2012 Sep-Oct;88(5):1184-90
references: 22335604
references: Eur J Cancer. 1999 Dec;35(14):2003-9
references: 10711242
references: Mutat Res. 2005 Apr 1;571(1-2):19-31
references: 15748635
references: Cancer Res. 2012 Jan 1;72(1):260-70
references: 22084399
references: Cancer Res. 2004 Nov 1;64(21):7756-65
references: 15520180
references: Exp Dermatol. 2003 Aug;12(4):445-52
references: 12930301
references: DNA Cell Biol. 2001 Dec;20(12):769-79
references: 11879570
references: Cancer Res. 2010 Mar 15;70(6):2415-23
references: 20215519
references: J Cutan Pathol. 2005 Mar;32(3):191-205
references: 15701081
references: J Biomed Sci. 2007 May;14(3):303-12
references: 17334833
references: Sci STKE. 2003 Jan 28;2003(167):RE2
references: 12554854
references: Carcinogenesis. 2005 Feb;26(2):331-42
references: 15550455