Sunlight UV-Induced Skin Cancer Relies upon Activation of the p38α Signaling Pathway

• Published in: Cancer research (Chicago, Ill.) Vol. 73; no. 7; pp. 2181 - 2188
• Main Authors: KANGDONG LIU, DONGHOON YU, ZIGANG DONG, CHO, Yong-Yeon, BODE, Ann M, WEIYA MA, KE YAO, SHENGQING LI, JIXIA LI, BOWDEN, G. Tim, ZIMING DONG
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.04.2013
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Blotting, Western; Cell Transformation, Neoplastic - radiation effects; Cells, Cultured; Dermatology; Genes, Dominant; Humans; Medical sciences; Mice; Mice, Hairless; Mice, Knockout; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); p38 Mitogen-Activated Protein Kinases - physiology; Pharmacology. Drug treatments; Phosphorylation - radiation effects; Protein Array Analysis; Signal Transduction - radiation effects; Skin - metabolism; Skin - pathology; Skin - radiation effects; Skin Neoplasms - etiology; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Sunlight - adverse effects; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Ultraviolet Rays - adverse effects; Signal transduction; Skin disease; Regulation(control); Signaling pathway; Activation; Skin; Malignant tumor; Cancer; Skin cancer
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-12-3408

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.