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树鼩( Tupaia belangeri chinensis )基底细胞癌模型的建立 Jiang, Li-Ping; Shen, Qiu-Shuo; Yang, Cui-Ping & Chen, Yong-Bin 基底细胞癌（basal cell carcinoma，BCC）是全世界最常见的皮肤肿瘤，发病率逐年升高。紫外线是BCC最主要的外界诱导致癌因素之一，Hedgehog（Hh）信号通路在皮肤细胞中的过度活化可以诱导BCC的产生，因此其信号通路中的许多关键分子被用来作为治疗BCC的靶点。然而，截止至今仍缺乏针对高转移性和晚期BCC的有效治疗手段，其中一个主要原因是许多药物筛选多以啮齿类动物作为模型检测其有效性，但在临床试验过程中常常被证明无效或副作用较大。因而迫切需要制备一个新型的动物模型，可以更好的模拟临床BCC表征，从而为未来新药的高效研发提供服务。中国科学院昆明动物所的研究成果显示，树鼩（Tupaia belangeri chinensis）在进化和许多生理生化指标上与人类亲缘关系相比啮齿类动物更近，利用其建立BCC动物模型具有独特优势。在本研究中，我们利用Hh信号通路Smoothened（Smo）的持续活化形式SmoA1，结合树鼩p53表达抑制shRNA，感染树鼩的皮肤激活Hh信号通路，病理和免疫组化分析结果显示，在较短时间内可以高效率地建立与人类BCC类似的树鼩BCC模型，该工作将为BCC的研究和治疗提供新型的动物模型。 树鼩；基底细胞癌；Hedgehog；动物模型

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Establishment of basal cell carcinoma animal model in Chinese tree shrew ( Tupaia belangeri chinensis ) Jiang, Li-Ping; Shen, Qiu-Shuo; Yang, Cui-Ping & Chen, Yong-Bin Abstract Basal cell carcinoma (BCC) is the most common skin cancer worldwide, with incidence rates continuing to increase. Ultraviolet radiation is the major environmental risk factor and dysregulation of the Hedgehog (Hh) signaling pathway has been identified in most BCCs. The treatment of locally advanced and metastatic BBCs is still a challenge and requires a better animal model than the widely used rodents for drug development and testing. Chinese tree shrews (Tupaia belangeri chinensis) are closely related to primates, bearing many physiological and biochemical advantages over rodents for characterizing human diseases. Here, we successfully established a Chinese tree shrew BCC model by infecting tail skins with lentiviral SmoA1, an active form of Smoothened (Smo) used to constitutively activate the Hh signaling pathway. The pathological characteristics were verified by immunohistochemical analysis. Interestingly, BCC progress was greatly enhanced by the combined usage of lentiviral SmoA1 and shRNA targeting Chinese tree shrew p53. This work provides a useful animal model for further BCC studies and future drug discoveries. Keywords Chinese tree shrew; Basal cell carcinoma; Hedgehog

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