Wnt/β-catenin and estrogen signaling converge in vivo
Wnt/β-catenin and estrogen signaling converge in vivo
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DOI：
10.1074/jbc.c400331200
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发表时间：
2004-09-24
影响因子：
4.8
通讯作者：
Kato, S
中科院分区：
文献类型：
--
作者：
Kouzmenko, AP;Takeyama, K;Kato, S
Wnt 和雌激素信号传导代表重要的调节途径，各自控制着广泛的生物过程。虽然越来越多的观察表明这些途径之间可能存在趋同，但尚未报道它们功能相互作用的直接证据。使用人类结肠癌细胞和乳腺癌细胞，我们发现雌激素受体（ER）α-和β-连环蛋白在相同的免疫复合物中沉淀，相互增强同源报告基因的反式激活，并相互招募到内源靶基因启动子中的同源反应元件。使用单独表达人类ERα或与代谢稳定的β-连环蛋白/犰狳突变体一起异位表达人类ERα的转基因果蝇，我们在体内证明了这些信号转导器之间的遗传相互作用。因此，我们在此提出了 Wnt 和雌激素信号通路之间通过 β-连环蛋白和 ERα 之间的功能相互作用进行串扰的第一个直接证据。
Wnt and estrogen signaling represent important regulatory pathways, each controlling a wide range of biological processes. While an increasing number of observations suggest potential convergence between these pathways, no direct evidence of their functional interaction has been reported. Using human colon and breast cancer cells, we found that estrogen receptor (ER) alpha- and beta-catenin precipitated within the same immunocomplexes, reciprocally enhanced the transactivation of cognate reporter genes, and were reciprocally recruited to cognate response elements in the promoters of endogenous target genes. Using transgenic Drosophila that ectopically expressed human ERalpha alone or together with metabolically stable beta-catenin/Armadillo mutants, we demonstrated genetic interaction between these signal transducers in vivo. Thus, we present here the first direct evidence of cross-talk between Wnt and estrogen signaling pathways via functional interaction between beta-catenin and ERalpha.