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Role of the transcription factor CREB in the regulation of cell proliferation in estrogen-responsive cells

转录因子CREB在雌激素反应性细胞增殖调节中的作用

基本信息

批准号：
17590198
负责人：
ARITA Jun
金额：
$ 2.24万
依托单位：
University of Yamanashi
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590198/
关键词：
estrogen cell proliferation anterior pituitary gland CREB

项目摘要

1 We generated Ad-TRE/MCREB.Tag, an adenovirus vector expressing the dominant negative CREB mutant MCREB. We verified morphologically and functionally the expression of MCREB protein.2 Infection with Ad-TRE/bgal as a negative control did not change forskolin-induced proliferation of lactotrophs whereas Ad-TRE/MCREB.Tag infection completely blocked forskolin-induced proliferation.3 Infection with Ad-TRE/MCREB.Tag partially suppressed stimulation of lactotroph proliferation by insulin-like growth factor-1 (IGF-1), a mitogen whose action is mediated by a signaling pathway distinct from the cyclic AMP/protein kinase A pathway.4 Treatment with forskolin or estradiol alone increased prolactin promoter activity and their combination further increased the promoter activity. Infection with Ad-TRE/bgal did not change basal or forskolin-induced levels of prolactin promoter activity whereas Ad-TRE/MCREB.Tag infection partially suppressed the basal and forskolin-induced levels.5 Intracellular cyclic AMP levels were markedly increased by forskolin treatment but not by IGF-1 treatment. Forskolin treatment markedly increased the proportion of phosphorylated CREB-immunoreactive lactotrophs at 20 min and up to 9 h whereas IGF-1 treatment modestly increased it only at 20 min and 1 h.

1构建了表达显性阴性CREB突变体MCREB的重组腺病毒载体Ad-tre/MCREB.Tag。我们从形态和功能上证实了MCREB蛋白的表达。2以Ad-tre/BGAL为阴性对照的感染并不改变Sklin诱导的催乳素诱导的细胞增殖，而Ad-Tre/MCREB感染则完全阻断了其诱导的增殖。3感染Ad-tre/MCREB后，Tag部分抑制了胰岛素样生长因子-1(IGF-1)对促乳素细胞增殖的刺激作用，IGF-1是一种有丝分裂原，其作用是通过与环状AMP/蛋白激酶A不同的信号通路来实现的。感染Ad-tre/BGAL不改变基础和Forsklin诱导的催乳素启动子活性水平，而Ad-Tre/MCREB感染部分抑制基础和Forsklin诱导的基础水平和Forsklin诱导的细胞内cAMP水平。Forsklin处理组在20min和9h时，CREB免疫反应阳性细胞的比例明显增加，而IGF-1处理组仅在20min和1h时略有增加。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Perinatal exposure to TCDD suppresses contextual fear conditioning-accompanied activation of cyclic AMP response element-binding protein in the hippocampal CAI region of male rats

围产期暴露于 TCDD 抑制雄性大鼠海马 CAI 区域中环境恐惧调节伴随的环 AMP 反应元件结合蛋白的激活

DOI：
发表时间：
2006
期刊：
Neuroscience Letters 398
影响因子：
0
作者：
Honma;K.;S.Hashimoto;T.Miyazaki;S.Honma.;T.Mitsui
通讯作者：
T.Mitsui

Estrogen actions on lactotroph proliferaiton are independent of a paracrine interaction with other pituitary cell types : a stud using lactotroph-enriched cells.

雌激素对泌乳素增殖的作用独立于与其他垂体细胞类型的旁分泌相互作用：一项使用富含泌乳素的细胞的研究。

DOI：
发表时间：
2007
期刊：
Endocrinology (in press)
影响因子：
0
作者：
Yamanaka;Y.;K.Honma;S.Hashimoto;N.Takatsu;T.Miyazaki;S.Honma.;M.Ishida et al.
通讯作者：
M.Ishida et al.

Pup removal suppresses estrogen-induced surges of LH secretion and activation of GnRH neurons in lactating rats.

去除幼崽可抑制哺乳期大鼠雌激素诱导的 LH 分泌激增和 GnRH 神经元激活。