Wagner Jörg, Lehmann Leane
Institute of Applied Biosciences, Section of Food Chemistry and Toxicology, University of Karlsruhe, Germany.
Mol Nutr Food Res. 2006 Apr;50(4-5):368-72. doi: 10.1002/mnfr.200500215.
The glycoprotein Wnt-7a participates in a signaling pathway that transmits information among uterine cell types. Disruption of this pathway by the transplacentally acting carcinogen diethylstilbestrol (DES) is associated with morphological abnormalities of the female reproductive tract (FRT). This raises the question whether estrogens in the diet might also interfere with this pathway. Therefore, this study investigated the influence of the steroid hormone 17beta-estradiol (E2), the mycotoxin zearalenone (ZEN), the soy phytoestrogen genistein (GEN), and DES on the expression of Wnt-7a in an endometrial adenocarcinoma cell line (Ishikawa cells) by reverse transcription/competitive PCR. In addition, the enzymatic activity of alkaline phosphatase (ALP) was determined, which is estrogen receptor (ER)-dependently regulated in Ishikawa cells. After treatment of Ishikawa cells with E2, ZEN, GEN, and DES, a decrease in the gene expression of Wnt-7a was observed. Maximum effect (50% reduction) was observed after treatment with concentrations that induced maximum expression of the ALP. Experiments in the presence of the ER antagonist (ICI 182,780) suggested that the ER is involved in the regulation of Wnt-7a in Ishikawa cells. In conclusion, interference with the expression of Wnt genes in the FRT might be a novel mechanism by which estrogens disrupt the function of the FRT.
糖蛋白Wnt-7a参与了一种在子宫细胞类型间传递信息的信号通路。经胎盘作用的致癌物己烯雌酚（DES）对该通路的破坏与女性生殖道（FRT）的形态异常有关。这就提出了一个问题，即饮食中的雌激素是否也可能干扰该通路。因此，本研究通过逆转录/竞争性PCR研究了甾体激素17β-雌二醇（E2）、霉菌毒素玉米赤霉烯酮（ZEN）、大豆植物雌激素染料木黄酮（GEN）和DES对子宫内膜腺癌细胞系（Ishikawa细胞）中Wnt-7a表达的影响。此外，还测定了碱性磷酸酶（ALP）的酶活性，其在Ishikawa细胞中受雌激素受体（ER）依赖性调节。用E2、ZEN、GEN和DES处理Ishikawa细胞后，观察到Wnt-7a基因表达下降。在用诱导ALP最大表达的浓度处理后观察到最大效应（降低50%）。在存在ER拮抗剂（ICI 182,780）的情况下进行的实验表明，ER参与了Ishikawa细胞中Wnt-7a的调节。总之，干扰FRT中Wnt基因的表达可能是雌激素破坏FRT功能的一种新机制。
