Identification of novel estrogen receptor α target gene and its function in endometrial cancer

新型雌激素受体α靶基因的鉴定及其在子宫内膜癌中的作用

• 批准号: 20591936
• 负责人: UTSUNOMIYA HIROKI
• 金额: $ 3万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591936/
• 关键词: Estrogen receptor; 子宮内膜癌; クロマチン免疫沈降; GRIP1; Estroen recetor; エストロゲン受容体; Erα; クロマチン免疫沈降(ChIP)クローニング; エストロゲン; Glutamate receptor interacting protein 1 (GR1P1)

Significant progress has been made in understanding the role of ERα as a transcription factor that regulates the expression of target genes by directly binding to an estrogen response element or by association with other transcription factors on promoter targets. Until recently, however, little had been known about the distribution of ERα-binding sites within the genome and the identity of genes regulated by these cis-acting elements. Our aims were to determine the nature of ERα binding relative to the structure of a gene and increase our understanding of ERα action in Ishikawa endometrial cancer cell line.Here, we used ChIP cloning technique and identified 47 ERα target loci in Ishikawa cells. The great majority of the binding sites were located in either introns or far distant to coding regions of genes. Among estradiol-induced genes, GRIP1 was found to increase cell survival by significantly reducing apoptosis in Ishikawa cells.Our findings suggest that at least a subset of these genes may play important biological roles in endometrial cancer.

ERα作为一种转录因子，通过直接与雌激素反应元件结合或与启动子靶点上的其他转录因子结合来调节靶基因的表达，其作用的研究已取得了重大进展。然而，直到最近，人们对ERα结合位点在基因组中的分布以及受这些顺式作用元件调控的基因的身份知之甚少。本研究采用ChIP克隆技术，在石川子宫内膜癌细胞系中筛选出47个ERα靶位点，并对ERα在石川子宫内膜癌细胞系中的作用机制进行了研究。绝大多数结合位点位于基因的内含子中或远离编码区。在雌二醇诱导的基因中，GRIP 1被发现通过显著减少石川细胞的凋亡来增加细胞存活。我们的研究结果表明，这些基因中至少有一个子集可能在子宫内膜癌中发挥重要的生物学作用。

项目成果

17Beta-hydroxysteroid dehydrogenase-2 deficiency and progesterone resistance in endometriosis.

• DOI: 10.1055/s-0029-1242992
• 发表时间: 2010-01-01
• 期刊: Seminars in reproductive medicine
• 影响因子: 2.7
• 作者: Bulun, Serdar E;Cheng, You-Hong;Su, Emily J
• 通讯作者: Su, Emily J

Steroidogenic factor-1 and endometriosis

• DOI: 10.1016/j.mce.2008.12.012
• 发表时间: 2009-03-05
• 期刊: MOLECULAR AND CELLULAR ENDOCRINOLOGY
• 影响因子: 4.1
• 作者: Bulun, Serdar E.;Utsunomiya, Hiroki;Xue, Qing
• 通讯作者: Xue, Qing

Estrogen receptor-beta, estrogen receptor-alpha, and progesterone resistance in endometriosis.

• DOI: 10.1055/s-0029-1242991
• 发表时间: 2010-01
• 期刊: Seminars in reproductive medicine
• 影响因子: 2.7
• 作者: Bulun SE;Cheng YH;Pavone ME;Xue Q;Attar E;Trukhacheva E;Tokunaga H;Utsunomiya H;Yin P;Luo X;Lin Z;Imir G;Thung S;Su EJ;Kim JJ
• 通讯作者: Kim JJ

Upstream Stimulatory Factors Regulate Steroidogenic Factor-1 Expression in Endometriosis.

上游刺激因子调节子宫内膜异位症中类固醇生成因子 1 的表达。

• 发表时间: 2008
• 期刊: Mol Endocrinol. 22
• 作者: Utsunomiya H;Bulun SE;et al.
• 通讯作者: et al.

Total laparoscopic conservative surgery for an intramural ectopic pregnancy.

全腹腔镜保守性手术治疗壁内异位妊娠。

• 发表时间: 2011
• 期刊: Diag Therap Endoscopy. (In press)
• 作者: Nabeshima H;Utsunomiya H;et al.
• 通讯作者: et al.