Rhiemeier Verena, Breitenbach Ute, Richter Karl Hartmut, Gebhardt Christoffer, Vogt Ingeborg, Hartenstein Bettina, Fürstenberger Gerhard, Mauch Cornelia, Hess Jochen, Angel Peter
Division of Signal Transduction and Growth Control, German Cancer Research Center, Heidelberg, Germany.
Am J Pathol. 2006 Apr;168(4):1354-64. doi: 10.2353/ajpath.2006.050871.
Homeostasis of stratified epithelia, such as the epidermis of the skin, is a sophisticated process that represents a tightly controlled balance between proliferation and differentiation. Alterations of this balance are associated with common human diseases including cancer. Here, we report the cloning of a novel cDNA sequence, from mouse back skin, that is induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and codes for a hitherto unknown aspartic proteinase-like protein (Taps). Taps represents a potential AP-1 target gene because TPA-induced expression in epidermal keratinocytes critically depends on c-Fos, and co-treatment with dexamethasone, a potent inhibitor of AP-1-mediated gene regulation, resulted in impaired activation of Taps expression. Taps mRNA and protein are restricted to stratified epithelia in mouse embryos and adult tissues, implicating a crucial role for this aspartic proteinase-like gene in differentiation and homeostasis of multilayered epithelia. During chemically induced carcinogenesis, transient elevation of Taps mRNA and protein levels was detected in benign skin tumors. However, its expression is negatively associated with dedifferentiation and malignant progression in squamous cell carcinomas of the skin. Similar expression was observed in squamous skin tumors of patients, suggesting that detection of Taps levels represents a novel strategy to discriminate the progression state of squamous skin cancers.
分层上皮组织（如皮肤表皮）的稳态是一个复杂的过程，代表着增殖与分化之间严格控制的平衡。这种平衡的改变与包括癌症在内的常见人类疾病相关。在此，我们报告从小鼠背部皮肤克隆出一个新的cDNA序列，它由佛波酯12 - O - 十四酰佛波醇 - 13 - 乙酸酯（TPA）诱导产生，编码一种迄今未知的天冬氨酸蛋白酶样蛋白（Taps）。Taps代表一个潜在的AP - 1靶基因，因为TPA诱导的表皮角质形成细胞中的表达关键依赖于c - Fos，并且与地塞米松（一种AP - 1介导的基因调控的有效抑制剂）共同处理会导致Taps表达的激活受损。Taps mRNA和蛋白在小鼠胚胎及成年组织的分层上皮组织中受限，这暗示这个天冬氨酸蛋白酶样基因在多层上皮组织的分化和稳态中起关键作用。在化学诱导的致癌过程中，在良性皮肤肿瘤中检测到Taps mRNA和蛋白水平的短暂升高。然而，其表达与皮肤鳞状细胞癌的去分化和恶性进展呈负相关。在患者的鳞状皮肤肿瘤中也观察到类似的表达，这表明检测Taps水平代表一种区分鳞状皮肤癌进展状态的新策略。
