Effects of UVB on E prostanoid receptor expression in murine skin.

Prostaglandin E2 (PGE2) upregulation in response to UV light exposure is a significant factor in the development of non-melanoma skin cancer. It is known that PGE2 signals via the E prostanoid receptors, EP1-4, but the role that each receptor plays in skin carcinogenesis is unclear. Immunohistochemical analysis of EP receptor staining in unirradiated and UVB-exposed SKH-1 mouse skin demonstrated the localization of EP1 and EP2 to the plasma membrane of differentiated epidermal keratinocytes. In contrast, the EP3 receptor localized to the basal layer of the epidermis in unirradiated skin and throughout the epidermis in UVB-exposed skin. In unirradiated skin, cytoplasmic EP4 staining was seen throughout the epidermis, in dermal leukocytes, and in vascular endothelium. However, UVB exposure resulted in relocalization of the EP4 receptor to the plasma membrane of keratinocytes, with no change in the dermal staining pattern. In tumors isolated from UVB-exposed mice, EP1 and EP2 staining was detected in the more differentiated cells surrounding keratin pearls, whereas EP3 and EP4 were detectable throughout the tumors. Differential expression of the EP receptors suggests that each receptor may play a distinct role in skin tumor development.