title: Pathobiology of actinic keratosis: ultraviolet-dependent keratinocyte proliferation.
abstract: Actinic keratoses are proliferations of transformed neoplastic keratinocytes in the epidermis that are the result of cumulative ultraviolet (UV) radiation from sun exposure. They are commonly found on sites of sun-exposed skin such as the face, balding scalp, and back of the hand. Although UV exposure does exert certain beneficial effects on the skin, excessive exposure to UV radiation induces multiple cascades of molecular signaling events at the cellular level that produce inflammation, immunosuppression, failure of apoptosis, and aberrant differentiation. Cumulatively, these actions result in mutagenesis and, ultimately, carcinogenesis. This article provides a brief overview of the key mediators that are implicated in the pathobiology of actinic keratosis. Three evolutionary possibilities exist for these keratoses in the absence of treatment: (1) spontaneous remission, which can be common; (2) remaining stable, without further progression; or (3) transformation to invasive squamous cell carcinoma, which may metastasize. Because the effects of UV radiation on the skin are complex, it is not yet fully clear how all of the mediators of actinic keratosis progression are interrelated. Nonetheless, some represent potential therapeutic targets, because it is clear that directing therapy to the effects of UV radiation at a number of different levels could interrupt and possibly reverse the mechanisms leading to malignant transformation.
authors.affiliation: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Berman
authors.forename: Clay J
authors.initials: CJ
authors.lastname: Cockerell
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000209:etiology; D049109:Cell Proliferation / Q000528:radiation effects*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D004247:DNA / Q000528:radiation effects; D006801:Humans; D007108:Immune Tolerance / Q000528:radiation effects; D007249:Inflammation / Q000503:physiopathology; D015603:Keratinocytes / Q000473:pathology* / Q000528:radiation effects; D055623:Keratosis, Actinic / Q000209:etiology / Q000473:pathology*; D010972:Platelet Activating Factor / Q000502:physiology; D015398:Signal Transduction / Q000528:radiation effects; D012867:Skin / Q000473:pathology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology / Q000473:pathology; D013472:Sunlight / Q000009:adverse effects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014560:Urocanic Acid / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D010972:Platelet Activating Factor; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D004247:DNA; D014560:Urocanic Acid