Pathobiology of actinic keratosis: Ultraviolet-dependent keratinocyte proliferation

      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.

      Key words

      Abbreviations used:

      AK ( actinic keratosis), BRG1 ( brahma-related gene 1), BRM ( brahma), COX ( cyclo-oxygenase), EGFR ( epidermal growth factor receptor), Foxp3 ( forkhead box p3), HPV ( human papillomavirus), IL ( interleukin), MIF ( macrophage migration inhibitory factor), MMP ( matrix metalloproteinase), PAF ( platelet-activating factor), PKC ( protein kinase C), ROS ( reactive oxygen species), SCC ( squamous cell carcinoma), TLR ( toll-like receptor), Tregs ( regulatory T cells), TSG ( tumor suppressor gene), UCA ( urocanic acid), UV ( ultraviolet)
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