Dss1: A Novel Tpa-inducible Gene Product

表皮是由具有低增殖能力的转运放大细胞和高度增殖的干细胞组成的快速更新的组织，其用于维持组织稳态。用肿瘤促进刺激物如12-O-十四烷酰基佛波醇-13-乙酸酯（TPA）、皮肤创伤或UV辐射暴露重复治疗Tg.AC转基因（v-Ha-ras，zetaglobin启动子）小鼠，导致诱导增生并最终产生表皮乳头状瘤，其中一些进展为鳞状细胞癌（SCC）。TPA对小鼠皮肤的作用被认为是由表观遗传机制介导的，所述表观遗传机制涉及起始细胞的增殖和分化的改变。大量的证据表明，皮肤的起始致癌物靶细胞最有可能是角质形成干细胞（KSC）。TPA特异性启动相关效应基因已经发展到包括至少30种，其中包括反式转录因子AP-1、原癌基因c-myc和c-fos、细胞受体PKC和编码蛋白酶的基因，包括胶原酶和纤溶酶原激活物等，但皮肤肿瘤形成的分子机制仍不清楚。这项研究涉及TPA诱导的皮肤肿瘤发生的其他基因。

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.