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

• 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

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 我们生成了 Ad-TRE/MCREB.Tag，这是一种表达显性失活 CREB ​​突变体 MCREB ​​的腺病毒载体。我们从形态和功能上验证了 MCREB ​​蛋白的表达。2 作为阴性对照，Ad-TRE/bgal 感染不会改变毛喉素诱导的泌乳素细胞增殖，而 Ad-TRE/MCREB.Tag 感染完全阻断毛喉素诱导的增殖。3 Ad-TRE/MCREB.Tag 感染部分抑制了毛喉素诱导的泌乳素增殖刺激。 胰岛素样生长因子-1 (IGF-1) 是一种有丝分裂原，其作用由不同于环 AMP/蛋白激酶 A 途径的信号途径介导。4 单独使用毛喉素或雌二醇治疗会增加催乳素启动子活性，而它们的组合会进一步增加启动子活性。 Ad-TRE/bgal 感染不会改变基础或毛喉素诱导的催乳素启动子活性水平，而 Ad-TRE/MCREB.Tag 感染部分抑制基础和毛喉素诱导的水平。 5 细胞内环 AMP 水平通过毛喉素处理显着增加，但通过 IGF-1 处理则没有。 Forskolin 处理在 20 分钟和 9 小时内显着增加磷酸化 CREB ​​免疫反应性泌乳素的比例，而 IGF-1 处理仅在 20 分钟和 1 小时时适度增加。

项目成果

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

• 发表时间: 2006
• 期刊: Neuroscience Letters 398
• 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。

• 发表时间: 2007
• 期刊: Endocrinology (in press)
• 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。

• 发表时间: 2006
• 期刊: Journal of Endocrinology 191
• 作者: Honma;K.;S.Masubuchi;S.Hashimoto;T.Endo;S.Honma.;A.Fukushima et al.
• 通讯作者: A.Fukushima et al.

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

去除幼仔可抑制雌激素诱导的哺乳期大鼠 LH 分泌激增和 GnRH 神经元激活

• 发表时间: 2006
• 期刊: Journal of Endocrinology 191
• 作者: Hasegawa I;Niisato N;A.Fukushima
• 通讯作者: A.Fukushima

Estrogen actions on lactotroph proliferaiton are independent of a paracrine interaction with other pituitary cell types : a study 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。

• 发表时间: 2007
• 期刊: Endocrinology (in press)
• 作者: Yamanaka;Y. et al.;M.Ishida
• 通讯作者: M.Ishida