Li Zhong-Lian, Ueki Ken, Kumagai Koji, Araki Ryoji, Otsuki Yoshinori
Department of Anatomy and Biology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
Med Mol Morphol. 2014 Mar;47(1):43-53. doi: 10.1007/s00795-013-0043-y. Epub 2013 May 11.
The estrogen-estrogen receptor (ER) signaling pathway plays crucial physiologic roles in not only the control of reproduction, but also in the generation of cancer in the breast and uterus. While some ER target genes have been identified containing the estrogen-responsive element (ERE), others are activated eventually by ER via protein-protein interaction without binding to ERE. In a previous study, we identified that the proliferative phase-specific expression of the bcl-2 gene in glandular cells could be regulated by the binding of c-Jun to its motifs in the promoter. Results from our present study indicate that the menstrual cyclic expression of bcl-2 could be controlled by either direct binding of ERα to ERE in the c-Jun promoter or the interaction of ERα with c-Jun that binds to its motifs in the bcl-2 gene. Intriguingly, the transcriptionally active form of c-Jun phosphorylated at Ser63 was identified binding to its motifs in the bcl-2 gene in a menstrual cyclic non-specific manner. Our study revealed a novel mechanism that transcriptionally regulates the expression of bcl-2 in the normal human endometrium.
雌激素-雌激素受体（ER）信号通路不仅在生殖控制中发挥关键的生理作用，而且在乳腺癌和子宫癌的发生中也起着重要作用。虽然已经鉴定出一些含有雌激素反应元件（ERE）的ER靶基因，但其他一些基因最终是通过ER通过蛋白质-蛋白质相互作用而被激活，而不与ERE结合。在先前的一项研究中，我们发现腺细胞中bcl-2基因的增殖期特异性表达可通过c-Jun与其启动子中的基序结合来调节。我们目前的研究结果表明，bcl-2的月经周期表达可通过ERα直接与c-Jun启动子中的ERE结合或ERα与结合在bcl-2基因基序上的c-Jun相互作用来控制。有趣的是，在Ser63处磷酸化的具有转录活性的c-Jun形式被发现以月经周期非特异性方式与其在bcl-2基因中的基序结合。我们的研究揭示了一种在正常人子宫内膜中转录调节bcl-2表达的新机制。
