The retinoic acid-related orphan receptors (RORs) regulate several physiological and pathological processes, including immune functions, development and cancer.,To study the potential role of RORs in melanoma progression, we analysed RORα and RORγ expression in nevi and primary melanomas and non-lesional skin and metastases in relation to melanoma clinico-pathomorphological features.,The expression of RORα and RORγ was lower in melanomas than in nevi and decreased during melanoma progression, with lowest levels found in primary melanomas at stages III and IV and in melanoma metastases.,Their expression correlated with pathomorphological pTNM parameters being low in aggressive tumors and being high in tumors showing histological markers of good prognosis.,Higher nuclear levels of RORα and RORγ and of cytoplasmic RORγ correlated with significantly longer overall and disease free survival time.,Highly pigmented melanomas showed significantly lower level of nuclear RORs.,This study shows that human melanoma development and aggressiveness is associated with decreased expression of RORα and RORγ, suggesting that RORs could be important in melanoma progression and host responses against the tumor.,Furthermore, it suggests that RORα and RORγ might constitute a novel druggable target in anti-melanoma management using tumor suppressor gene therapy restoring their normal functions.
Exposure to sunlight is the major cause of skin cancer.,Ultraviolet radiation (UV) from the sun causes damage to DNA by direct absorption and can cause skin cell death.,UV also causes production of reactive oxygen species that may interact with DNA to indirectly cause oxidative DNA damage.,UV increases accumulation of p53 in skin cells, which upregulates repair genes but promotes death of irreparably damaged cells.,A benefit of sunlight is vitamin D, which is formed following exposure of 7-dehydrocholesterol in skin cells to UV.,The relatively inert vitamin D is metabolized to various biologically active compounds, including 1,25-dihydroxyvitamin D3.,Therapeutic use of vitamin D compounds has proven beneficial in several cancer types, but more recently these compounds have been shown to prevent UV-induced cell death and DNA damage in human skin cells.,Here, we discuss the effects of vitamin D compounds in skin cells that have been exposed to UV.,Specifically, we examine the various signaling pathways involved in the vitamin D-induced protection of skin cells from UV.