Dss1: A Novel Tpa-inducible Gene Product

Environmental Health Sciences

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Abstract

The epidermis is a rapidly renewing tissue composed of transit amplifying cells having a low proliferative capacity and highly proliferative stem cells, which serve to maintain tissue homeostasis. Repeated treatment of Tg.AC transgenic (v-Ha-ras, zetaglobin promoter) mice with a tumor promoting stimulus such as 12-O-tetradecanoylphorbol-13-acetate (TPA), wounding of the skin or UV radiation exposure results in the induction of hyperplasia and eventually the outgrowth of epidermal papillomas, some of which progress to squamous cell carcinomas (SCCs). The effects of TPA on mouse skin are thought to be mediated by epigenetic mechanisms involving alterations in the proliferation and differentiation of initiated cells. A large body of evidence strongly indicates that the initiated carcinogen target cells of skin are most likely keratinocyte stem cells (KSCs). TPA-specific promotion-relevant effector genes have grown to include at least 30, among them, transacting transcription factor AP-1, proto-oncogenes c-myc and c-fos, cellular receptor PKC, and genes encoding proteases, including collagenase and plasminogen activator etc., but the molecular mechanism(s) of skin tumor formation remains unclear. This study addresses additional genes involved in TPA-induced skin tumorigenesis.