We analyzed the role of WIF1 in normal and acanthotic epidermis of 12-O-tetradecanoylphorbol-13-acetate (TPA) or all-trans-retinoic acid (ATRA)-treated and basal cell carcinoma (BCC)-bearing mice. WIF1 protein is located in the follicular infundibulum and interfollicular epidermis (IFE) in murine back skin. Within the hyperplastic epidermis of TPA- or ATRA-treated or BCC-bearing murine skin, WIF1 and Keratin 10 overlap in Ki67^⁻ suprabasal layers, while basal epidermal layers expressing Ki67, and BCCs expressing Wif1 mRNA, are free of WIF1 protein. This is similar in human skin, with the exception that WIF1 protein is found in single Ki67^⁻ basal epidermal cells in normal skin and additionally in Ki67⁺ cells in acanthotic skin. Wif1-deficiency enhances acanthosis of the murine BCC-associated epidermis, which is accompanied by an increase of Ki67⁺ and of Sca-1⁺ basal cells. WIF1 overexpression in allografted BCC-derived keratinocytes prevents growth and keratinization, involving enhanced phosphorylation of protein kinase C and extracellular signal–regulated kinase 1 and arguably factors secreted by the in vivo environment. In summary, WIF1 protein marks suprabasal layers in the normal IFE. It is also present in the epidermis overlaying BCCs where it diminishes proliferation of basal cells and production of differentiating suprabasal cells. In addition, WIF1 can prevent proliferation and keratinization of BCC-related keratinocytes.

我们分析了WIF1在正常和棘皮表皮的12-O-十四烷酰phorbol-13-乙酸盐（TPA）或全反式维甲酸（ATRA）治疗的和基底细胞癌（BCC）的小鼠中的作用。WIF1蛋白位于鼠背皮肤的卵泡漏斗和小泡间表皮（IFE）中。在经TPA或ATRA处理或带有BCC的小鼠皮肤的增生表皮中，WIF1和角蛋白10在Ki67 ^ra基底上层重叠，而表达Ki67的基底表皮层和表达Wif1 mRNA的BCC不含WIF1蛋白。这与人类皮肤相似，只是在正常皮肤的单个^Ki67⁻基底表皮细胞中以及在Ki67 ⁺棘皮细胞中的细胞。Wif1缺乏会增强鼠BCC相关表皮的棘皮症，并伴有Ki67 ⁺和Sca-1 ⁺基底细胞的增加。在同种异体移植BCC衍生的角质形成细胞中WIF1的过量表达可阻止生长和角化，包括增强蛋白激酶C和细胞外信号调节激酶1的磷酸化作用，以及可能由体内环境分泌的因子。总之，WIF1蛋白标记正常IFE中的基底上层。它也存在于表皮覆盖的BCC中，在这里它会减少基底细胞的增殖和分化的上基底细胞的产生。此外，WIF1可以防止BCC相关角质形成细胞的增殖和角化。