Role of mTOR signaling pathway for the growth and proliferation of uterine leiomyoma

mTOR信号通路在子宫肌瘤生长和增殖中的作用

• 批准号: 23592393
• 负责人: ISHIKAWA Hiroshi
• 金额: $ 3.24万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592393/
• 关键词: 子宮筋腫; mTOR; 動物モデル; xenograft; 免疫不全マウス; hypoxia; HIF1; 重症免疫不全マウス; Hypoxia; メトホルミン; 移植モデル

We investigated the role of mammalian target of rapamycin (mTOR) signaling pathway for the growth and proliferation of uterine leimyoma; however, we did not find any overexpression of protein levels as well as mRNA levels of mTOR signaling pathway-related genes in uterine leiomyoma compared with those in myometrial tissues.Next, we established a novel in vivo xenograft model for uterine leiomyoma, and evaluated its characters. The non-obese diabetic/severe combined immunodeficient murine xenograft model has shown a sex-steroid dependent growth of xenograft beneath the kidney capsule, a positive expression for both estrogen and progesterone receptors, and a similar representative gene expression compared with original leiomyoma tissue. In this model, we use only non-genetic manupilated primary cultured leiomyoma cells; therefore, we believe this model is a good tool for the research and the development of new therapies for uterine leiomyoma.

我们研究了哺乳动物靶向雷帕霉素(MTOR)信号通路在子宫肌瘤生长和增殖中的作用，但没有发现与子宫肌瘤组织相比mTOR信号通路相关基因的蛋白水平和mRNA水平的过表达。非肥胖糖尿病/严重联合免疫缺陷小鼠异种移植模型显示，异基因移植物在肾被膜下呈性别激素依赖性生长，雌激素和孕激素受体均为阳性表达，与原始肌瘤组织相比具有相似的代表性基因表达。在该模型中，我们只使用非遗传性人工毛发原代培养的子宫肌瘤细胞；因此，我们认为该模型是研究和开发子宫肌瘤新疗法的良好工具。

项目成果

Nonobese diabetic/severe combined immunodeficient murine xenograft model for human uterine leiomyoma.

用于人子宫肌瘤的非肥胖糖尿病/严重联合免疫缺陷小鼠异种移植模型。

• DOI: 10.1016/j.fertnstert.2014.01.054
• 发表时间: 2014
• 期刊: Fertility and Sterility
• 影响因子: 6.7
• 作者: Wang G;Ishikawa H;Sone K;Kobayashi T;Kim JJ;Kurita T;Shozu M.
• 通讯作者: Shozu M.

子宮筋腫の免疫不全マウス移植モデルにおける、宿主と移植方法の検討

子宫肌瘤免疫缺陷小鼠移植模型宿主及移植方法的研究

• 发表时间: 2013
• 作者: 石川博士;王 桂文;曽根国瑞;大見健二;川野みどり;木原真紀;生水真紀夫
• 通讯作者: 生水真紀夫

子宮筋腫低酸素培養下におけるHypoxia inducible factor-1αの発現低下

子宫肌瘤缺氧培养中缺氧诱导因子1α表达降低

• 发表时间: 2013
• 作者: 石川博士;川野みどり;王桂文;河原井麗正;大見健二;生水真紀夫
• 通讯作者: 生水真紀夫

Altered expression of hypoxia inducible factor-1 in uterine leiomyoma under hypoxic and normoxic condition.

缺氧和常氧条件下子宫肌瘤缺氧诱导因子-1表达的改变。

• 发表时间: 2012
• 作者: Ishikawa H;Kawarai Y;Takizawa S;Wang GW;Shozu M
• 通讯作者: Shozu M

Serous Tubal Intraepithelial Carcinoma in a Japanese Woman with a Deleterious BRCA1 Mutation

一名患有 BRCA1 有害突变的日本女性患浆液性输卵管上皮内癌

• DOI: 10.1093/jjco/hyu035
• 发表时间: 2014
• 期刊: Jpn J Clin Oncol
• 影响因子: 2.4
• 作者: Ishikawa H;Kiyokawa T;Utsuno E;Matsushita K;Nomura F;Shozu M
• 通讯作者: Shozu M