Oral communication, PS5 / C68

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Novel role of melanocytic RXR alpha /RXR beta in UV irradiation induced melanocyte homeostasis

Retinoid-X-Receptors (RXRs) alpha, beta, and gamma are members of the nuclear hormone receptor (NR) superfamily, and act as central coordinators of cell signal transduction through heterodimerization with several other NRs. In malignant human melanoma samples, loss of RXRα expression has been previously observed both in the melanoma cells themselves (Chakravarti et al, 2007) and in adjacent epidermal keratinocytes (Hyter et al, 2010). Previously, epidermal-specific ablation of RXRalpha in a mouse model has been shown to promote increased melanocyte proliferation after UV radiation (Wang et al, 2010) and increased susceptibility to malignant melanomas (Hyter et al, 2010). We recently found that Cre-LoxP mediated selective ablation of RXRalpha and RXRbeta specifically in melanocytes of skin results in an increase in apoptosis in non-melanocytic cells in dermal layer following UV irradiation. UV induced interferon-y production, preferably by macrophages, controls melanocyte activation and has protective effects on survival of melanoma cells in vivo (Zaidi et al., 2010). Interestingly, expression of interferon-γ was found to be downregulated in dermal layer following UV radiation, suggesting possible defects in activation/recruitment of macrophages and other inflammatory cells. Additionally, melanocytic ablation of RXRalpha / RXRbeta resulted in a decreased percentage of apoptotic melanocytes following UV radiation, suggesting an increased survival of cells following DNA damage. That reduced apoptosis can contribute to increased incorporation of mutation into the melanocytes and increased susceptibility of UV induced melanoma formation in the long-term. References: Chakravarti, N., Lotan, R., Diwan, A.H., Warneke, C.L., Johnson, M.M., Prieto, V.G. (2007), Clin Cancer Res, 13, 4817-24. Hyter, S., Bajaj, G., Liang, X, Barbacid, M., Indra G., Indra, A.K. (2010). Pigment Cell and Melanoma Research. Oct: 23 (5): 635-648. Wang Z., Coleman, D.J., Bajaj, G., Liang X., Ganguli-Indra, G., Indra, A.K. (2011). JID (NPG). Jan;131(1):177-87. Epub 2010 Oct 14. Zaidi MR, Davis S, Noonan FP, Graff-Cherry C, Hawley TS, Walker RL, Feigenbaum L, Fuchs E, Lyakh L, Young HA, Hornyak TJ, Arnheiter H, Trinchieri G, Meltzer PS, De Fabo EC, Merlino G.Nature. 2011 Jan 27;469(7331):548-53.

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