Ultraviolet radiation-induced inflammation activates β-catenin signaling in mouse skin and skin tumors

  • Authors:
    • Ram Prasad
    • Santosh K. Katiyar
  • View Affiliations

  • Published online on: January 23, 2014     https://doi.org/10.3892/ijo.2014.2275
  • Pages: 1199-1206
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Abstract

UVB-induced inflammation, in particular the overexpression of cyclooxygenase-2 (COX-2) and prostaglandin (PG) E2, has been implicated in photocarcinogenesis. UVB-induced COX-2 has been associated with β-catenin signaling in keratinocytes. However, a definitive role for COX-2 in the activation of β-catenin signaling as well as its role in UVB-induced skin tumors has not been established. We report that exposure of the skin to UVB resulted in a time- and dose-dependent activation of β-catenin in C3H/HeN mice. This response was COX-2-dependent as UVB-exposed COX-2-deficient mice exhibited significantly lower levels of UVB-induced activation of β-catenin. Moreover, treatment of mice with indomethacin, a COX-2 inhibitor, and an EP2 antagonist inhibited UVB-induced β-catenin signaling. Exposure of SKH-1 hairless mice to UVB radiation (180 mJ/cm2) 3 times a week for 24 weeks resulted in activation of β-catenin signaling in UVB-irradiated skin as well as UVB-induced skin tumors. Concomitantly, the levels of CK1α and GSK-3β, which are responsible for β-catenin signaling, were reduced while the levels of c-Myc and cyclin D1, which are downstream targets of β-catenin, were increased. To further verify the role of UVB-induced inflammation in activation of β-catenin signaling, a high-fat-diet model was used. Administration of high-fat diet exacerbated UVB-induced inflammation. Administration of the high-fat diet enhanced β-catenin signaling and the levels of its downstream targets (c-Myc, cyclin D1, cyclin D2, MMP-2 and MMP-9) in UVB-exposed skin and skin tumors in SKH-1 mice. These data suggest that UV-induced COX-2/PGE2 stimulates β-catenin signaling, and that β-catenin activation may contribute to skin carcinogenesis.
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2014-April
Volume 44 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Prasad R and Prasad R: Ultraviolet radiation-induced inflammation activates β-catenin signaling in mouse skin and skin tumors. Int J Oncol 44: 1199-1206, 2014
APA
Prasad, R., & Prasad, R. (2014). Ultraviolet radiation-induced inflammation activates β-catenin signaling in mouse skin and skin tumors. International Journal of Oncology, 44, 1199-1206. https://doi.org/10.3892/ijo.2014.2275
MLA
Prasad, R., Katiyar, S. K."Ultraviolet radiation-induced inflammation activates β-catenin signaling in mouse skin and skin tumors". International Journal of Oncology 44.4 (2014): 1199-1206.
Chicago
Prasad, R., Katiyar, S. K."Ultraviolet radiation-induced inflammation activates β-catenin signaling in mouse skin and skin tumors". International Journal of Oncology 44, no. 4 (2014): 1199-1206. https://doi.org/10.3892/ijo.2014.2275