| First Author | Prasad R | Year | 2014 |
| Journal | Int J Oncol | Volume | 44 |
| Issue | 4 | Pages | 1199-206 |
| PubMed ID | 24481495 | Mgi Jnum | J:305687 |
| Mgi Id | MGI:6705259 | Doi | 10.3892/ijo.2014.2275 |
| Citation | Prasad R, et al. (2014) Ultraviolet radiation-induced inflammation activates beta-catenin signaling in mouse skin and skin tumors. Int J Oncol 44(4):1199-206 |
| abstractText | 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 beta-catenin signaling in keratinocytes. However, a definitive role for COX-2 in the activation of beta-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 beta-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 beta-catenin. Moreover, treatment of mice with indomethacin, a COX-2 inhibitor, and an EP2 antagonist inhibited UVB-induced beta-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 beta-catenin signaling in UVB-irradiated skin as well as UVB-induced skin tumors. Concomitantly, the levels of CK1alpha and GSK-3beta, which are responsible for beta-catenin signaling, were reduced while the levels of c-Myc and cyclin D1, which are downstream targets of beta-catenin, were increased. To further verify the role of UVB-induced inflammation in activation of beta-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 beta-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 beta-catenin signaling, and that beta-catenin activation may contribute to skin carcinogenesis. |
