Nei H, Saito T, Yamasaki H, Mizumoto H, Ito E, Kudo R
Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Japan.
Mol Carcinog. 1999 Jul;25(3):207-18.
We have previously shown that the connexin (Cx) 26 and 32 genes are expressed during the secretory phase of the human endometrium and that their expression is downregulated during the proliferative phase, suggesting a role for intercellular transduction in cell growth control in human endometrium. To further study the possible role of cell-to-cell interaction in growth regulation, we immunohistochemically analyzed 80 endometrial samples (30 of normal endometrium, 20 of endometrial hyperplasia, and 30 of endometrial cancer) for the expression of E-cadherin; alpha-, beta-, and gamma-catenin; adenomatous polyposis coli (APC) protein, and sex-steroid hormone receptors at three points in the cells: the cell-to-cell border, the cytoplasm, and the nucleus. In this study, moderate or strong staining of beta-catenin in the nuclei was observed in 60.0% of endometrial hyperplasia samples and 30.0% of endometrial cancer samples, although the beta-catenin gene was mutated in only two of the nine samples that showed the intensive nuclear staining. Western blotting analysis showed that the samples that had intense nuclear staining of beta-catenin had much higher expression of beta-catenin than the samples that did not have nuclear staining. Furthermore, normal endometrium showed nuclear localization, especially in the mid- and late-proliferative and early-secreting phases of the menstrual cycle. The results suggest that the nuclear localization of beta-catenin observed in endometrial hyperplasia and endometrial cancer, as in other tumors, implies that beta-catenin/Wnt-1 signal transduction is highly activated in carcinogenesis of the endometrium as well as in normal physiological conditions.
我们之前已经表明，连接蛋白（Cx）26和32基因在人子宫内膜的分泌期表达，而在增殖期其表达下调，这表明细胞间转导在人子宫内膜细胞生长控制中发挥作用。为了进一步研究细胞间相互作用在生长调节中的可能作用，我们采用免疫组织化学方法分析了80份子宫内膜样本（30份正常子宫内膜样本、20份子宫内膜增生样本和30份子宫内膜癌样本）中E-钙黏蛋白、α-、β-和γ-连环蛋白、腺瘤性息肉病基因（APC）蛋白以及性甾体激素受体在细胞三个部位（细胞间边界、细胞质和细胞核）的表达情况。在本研究中，60.0%的子宫内膜增生样本和30.0%的子宫内膜癌样本中观察到细胞核内β-连环蛋白呈中度或强染色，尽管在9份显示细胞核强染色的样本中只有2份β-连环蛋白基因发生了突变。蛋白质印迹分析表明，细胞核内β-连环蛋白呈强染色的样本中β-连环蛋白的表达远高于无细胞核染色的样本。此外，正常子宫内膜显示出细胞核定位，尤其是在月经周期的增殖中期和后期以及分泌早期。结果表明，在子宫内膜增生和子宫内膜癌中观察到的β-连环蛋白的细胞核定位，与其他肿瘤一样，意味着β-连环蛋白/Wnt-1信号转导在子宫内膜癌发生过程中以及正常生理条件下均被高度激活。
