Lo Muzio Lorenzo, Pannone Giuseppe, Staibano Stefania, Mignogna Michele D, Grieco Michele, Ramires Pierangela, Romito Anna Maria, De Rosa Gaetano, Piattelli Adriano
Institute of Dental Sciences, University of Ancona, Italy.
Anticancer Res. 2002 Mar-Apr;22(2A):565-76.
The WNT gene family is a group of developmental genes involved in cell growth regulation, differentiation and organogenesis in both vertebrates and invertebrates. These genes are also involved in oncogenesis: beta-catenin, a component of the WNT pathway, has been reported to be involved in the genesis of numerous human cancers. WNT-1 pathway signaling is mediated via interactions between beta-catenin, a multifunctional protein playing an important role in cell-to-cell adhesion and gene expression, and members of the LEF-1/TCF family of transcription factors. The WNT signal stabilizes beta-catenin protein and determines its accumulation in the cytoplasm and nucleus.
In order to evaluate the role of WNT-1 in the neoplastic progression of basal cell carcinoma (BCC), an immunohistochemical and confocal study of its expression and its correlation with beta-catenin distribution was performed in 46 selected cases of BCCs of the head and neck region.
While normal skin showed a WNT-1-positive staining only of the cutaneous annexa and a few cells in the basal/parabasal layers, the areas of de-differentiated BCCs showed a high granular positive staining (50-80% of cells). On the other hand, normal skin was characterized by an intense membranous staining for beta-catenin, with a progressive displacement of the signal toward the periphery of the cells. In BCC the absence of membrane localization and cytosolic staining for beta-catenin were detected in de-differentiated cases. A significant correlation (by Pearson's analysis) between overexpression of WNT-1 and free pools of beta-catenins was observed in these tumors.
According to these data, the potential role of the WNT-1 gene in BCC seems to correlate with its ability to induce elevated cytoplasmic beta-catenin levels, suggesting that the WNT-1 gene can activate an intracellular signaling pathway involved in the process of cell transformation.
WNT基因家族是一组参与脊椎动物和无脊椎动物细胞生长调节、分化及器官形成的发育基因。这些基因也与肿瘤发生有关：据报道，WNT信号通路的一个组成部分β-连环蛋白参与了多种人类癌症的发生。WNT-1信号通路是通过β-连环蛋白（一种在细胞间黏附和基因表达中起重要作用的多功能蛋白质）与LEF-1/TCF转录因子家族成员之间的相互作用介导的。WNT信号使β-连环蛋白蛋白稳定，并决定其在细胞质和细胞核中的积累。
为了评估WNT-1在基底细胞癌（BCC）肿瘤进展中的作用，对46例头颈部BCC病例进行了免疫组织化学和共聚焦研究，以检测其表达情况及其与β-连环蛋白分布的相关性。
正常皮肤仅在皮肤附属器以及基底/副基底层的少数细胞中显示WNT-1阳性染色，而去分化的BCC区域则显示出高颗粒状阳性染色（50%-80%的细胞）。另一方面，正常皮肤的特征是β-连环蛋白呈强烈的膜染色，信号逐渐向细胞周边移位。在去分化的BCC病例中，检测到β-连环蛋白缺乏膜定位和胞质染色。在这些肿瘤中观察到WNT-1过表达与游离β-连环蛋白池之间存在显著相关性（通过Pearson分析）。
根据这些数据，WNT-1基因在BCC中的潜在作用似乎与其诱导细胞质β-连环蛋白水平升高的能力相关，这表明WNT-1基因可以激活参与细胞转化过程的细胞内信号通路。
