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Roles of estrogen receptors and protooncogenes in uterine cell proliferation.

雌激素受体和原癌基因在子宫细胞增殖中的作用。

基本信息

批准号：
06670042
负责人：
YAMASHITA Shuji
金额：
$ 1.34万
依托单位：
Keio Junior College of Nursing
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670042/
关键词：
estrogen receptor c-fos c-jun lactoferrin immunohistochemistry in situ hybridization uterus estrogen stimulation プロトオンコジーン c‐fos c‐jun in situ ハイゴリダイゼーションマウス免疫電顕

项目摘要

1) Localization of estrogen receptors (ER) in the nucleus of mouse uterine epitheliumLocalization of hormone occupied and unoccupied ER is investigated to clarify if ER translocate within the nucleus after hormone binding, using ultrathin frozen sections combined with the immunogold technique. Adult ovariectomized mice were injected with estradiol (E2) or saline and killed after 1 hr and the uteri were processed for the immunoelectron microscopy. No apparent changes in the structure of chromatin and ER localization were observed ; both unoccuoied and occupied ER were present in the dispersed and slightly condensed chromatin but not in the nucleolus and highly condensed chromatin. These results suggest that ER activate closely locating target genes without a marked intranuclear translocation.2) Hormonal induction of lactofferin (LF) in the uterine cellsTemporal localizaton of estrogen inducible secretory protein, LF was investigated in the uterus of ovariectomized mouse after E2 stimula … More tion. LF immunoreaction was detectable in the secretory pathways, i.e., in the rough surfaced endoplasmic reticulum, the Golgi apparatus and secretory vesicles of epithelial cells. Furthermore, ER were rapidly induced in the in the nucleolus showing a peak at 6-13 hr after E2 injection. These findings suggest that LF is one of early genes which is involved in the synthesis of ribosomes prior to the proliferation, although LF has been thought as a late gene and used as a maker of cytodifferentiation of epithelium.3) Hormonal induction of protooncogenes in the mouse uterusCell type specific and temporal expression of c-fos and c-jun protooncogenes was examined in the mouse uterus after E2 stimulation employing immunohistochemistry and in situ hybridization. The c-fos protein and mRNA were transiently expressed in the epithelial cells 2 hr after E2 injection. In contrast, E2 injection elicited a decrease of c-jun expression after 2-6 hr in the epithelial cells, however, it was increased in the stromal and myometrial muscle cells. In the endothelial cells of blood vessels, both c-fos and c-jun were transiently induced 1-2 hr after E2 stimulation. These results indicate that rapid and transit changes in the concentration of c-fos and c-jun proteins, which form transcription factor AP-1, may trigger the proliferation of uterine epithelium. Less

1)雌激素受体（ER）在小鼠子宫上皮细胞核内的定位本实验采用冰冻切片结合免疫胶体金技术，研究了雌激素结合后ER在细胞核内的定位。成年卵巢切除小鼠注射雌二醇（E2）或生理盐水，1小时后处死，子宫进行免疫电镜检查。染色质结构和ER定位无明显变化，未被占据和被占据的ER均存在于分散和轻度浓缩的染色质中，而不存在于核仁和高度浓缩的染色质中。这些结果表明，雌激素受体激活的靶基因定位密切，但没有明显的核内易位。2）子宫细胞中乳铁蛋白（LF）的激素诱导。 ...更多信息是的。LF免疫反应在分泌途径中可检测到，即，在粗面内质网、高尔基体和上皮细胞的分泌泡中。此外，E2注射后6-13小时，在核仁中迅速诱导ER，并出现高峰。这些结果表明LF是参与增殖前核糖体合成的早期基因之一，虽然LF被认为是一个晚期基因，并被用作上皮细胞分化的标志。3）激素诱导小鼠子宫原癌基因c-fos和c-fos的细胞类型特异性和时间表达采用免疫组织化学和原位杂交技术检测了E2刺激后小鼠子宫中Jun原癌基因的表达。注射E2后2 h，上皮细胞内出现c-fos蛋白和mRNA的瞬时表达。与此相反，E2注射引起c-jun表达减少后2-6小时在上皮细胞，但它在基质和肌层肌细胞增加。在血管内皮细胞中，c-fos和c-jun在E2刺激后1-2小时瞬时诱导。这些结果表明，形成转录因子AP-1的c-fos和c-jun蛋白浓度的快速和短暂变化可能触发子宫上皮的增殖。少