Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, P.O. Box 389, Smithville, TX 78957, USA.
Program in Toxicology and Pharmacology, College of Pharmacy, University of New Mexico Health Sciences Center, MSC 09 5360, 1 University of New Mexico, Albuquerque, NM 87131, USA.
J Clin Med. 2016 Feb 3;5(2):21. doi: 10.3390/jcm5020021.
The Slug transcription factor plays an important role in ultraviolet radiation (UVR)-induced skin carcinogenesis, particularly in the epithelial-mesenchymal transition (EMT) occurring during tumor progression. In the present studies, we investigated the role of Slug in two-stage chemical skin carcinogenesis. Slug and the related transcription factor Snail were expressed at high levels in skin tumors induced by 7,12-dimethylbenz[α]anthracene application followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment. TPA-induced transient elevation of Slug and Snail proteins in normal mouse epidermis and studies in Slug transgenic mice indicated that Slug modulates TPA-induced epidermal hyperplasia and cutaneous inflammation. Although Snail family factors have been linked to inflammation via interactions with the cyclooxygenase-2 (COX-2) pathway, a pathway that also plays an important role in skin carcinogenesis, transient TPA induction of Slug and Snail appeared unrelated to COX-2 expression. In cultured human keratinocytes, TPA induced Snail mRNA expression while suppressing Slug expression, and this differential regulation was due specifically to activation of the TPA receptor. These studies show that Slug and Snail exhibit similar patterns of expression during both UVR and chemical skin carcinogenesis, that Slug and Snail can be differentially regulated under some conditions and that in vitro findings may not recapitulate in vivo results.
Slug 转录因子在紫外线辐射（UVR）诱导的皮肤致癌作用中发挥着重要作用，尤其是在肿瘤进展过程中发生的上皮-间充质转化（EMT）中。在本研究中，我们研究了 Slug 在两阶段化学皮肤致癌中的作用。在应用 7,12-二甲基苯并[α]蒽后再用 12-O-十四烷酰佛波醇-13-乙酸酯（TPA）处理诱导的皮肤肿瘤中，Slug 和相关转录因子 Snail 的表达水平较高。TPA 诱导正常小鼠表皮中 Slug 和 Snail 蛋白的瞬时升高，以及 Slug 转基因小鼠的研究表明，Slug 调节 TPA 诱导的表皮增生和皮肤炎症。尽管 Snail 家族因子通过与环氧化酶-2（COX-2）途径相互作用与炎症有关，而该途径在皮肤致癌作用中也起着重要作用，但 Slug 和 Snail 的瞬时 TPA 诱导似乎与 COX-2 表达无关。在培养的人角质形成细胞中，TPA 诱导了 Snail mRNA 的表达，同时抑制了 Slug 的表达，这种差异调节是由于 TPA 受体的特异性激活。这些研究表明，Slug 和 Snail 在 UVR 和化学皮肤致癌作用中表现出相似的表达模式，Slug 和 Snail 在某些条件下可以被差异化调节，并且体外发现可能无法重现体内结果。
