title: Ultraviolet irradiation induces c-fos but not c-Ha-ras proto-oncogene expression in human epidermis.
abstract: The link between sun exposure and skin cancer is well established, but the mechanism of photocarcinogenesis is still incompletely understood. In vitro experimentation has shown that induction of the c-fos proto-oncogene occurs in cultured human keratinocytes after ultraviolet exposure, and c-Ha-ras mutations are commonly present in human skin neoplasms removed from chronically sun-exposed sites. In the present study, the effect of UV irradiation on the expression of these two proto-oncogenes was examined. The sun-protected volar forearm of six subjects was exposed to a standardized erythemogenic dose of solar-simulated light, and punch biopsies were obtained after 1 h and 24 h from the irradiated area and a nearby shielded area. Expression of c-fos, determined by in situ hybridization of histologic cross-sections, was detected in the basal and lower epidermal layers in all biopsies. However, at 1 h there was a marked increase that returned to baseline by 24 h. c-Ha-ras mRNA could not be detected by riboprobe hybridization in any of the biopsy specimens. Our data demonstrate transient induction of c-fos but not c-Ha-ras expression, at least at the timepoints studied, following a modest UV exposure in normal skin. This phenomenon may lead to the subsequent constitutive over-expression and super-inducibility of c-fos observed in cultured keratinocytes derived from photodamaged skin and may facilitate the development of skin cancer.
authors.affiliation: Department of Dermatology, Boston University School of Medicine, MA 02118.
authors.forename: P K
authors.initials: PK
authors.lastname: Roddey
authors.forename: M
authors.initials: M
authors.lastname: Garmyn
authors.forename: H Y
authors.initials: HY
authors.lastname: Park
authors.forename: J
authors.initials: J
authors.lastname: Bhawan
authors.forename: B A
authors.initials: BA
authors.lastname: Gilchrest
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004817:Epidermis / Q000737:chemistry / Q000502:physiology*; D015870:Gene Expression / Q000528:radiation effects*; D016762:Genes, fos / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger