Analysis of endometrial cancer development

子宫内膜癌发生发展分析

• 批准号: 17390452
• 负责人: KATO Kiyoko
• 金额: $ 10.71万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390452/
• 关键词: endometrial cancer; endometrium; stem cell; molecular target therapy; estrogen receptor; エストロゲンレセフター

1. We previously demonstrated that that the Ras/ER/MDM2 pathway was critical for NIH3T3 cell transformation. In this study, we examined the effect of blocking this pathway on cell growth in gynecologic cancer cells. (1) The MDM2 level was enhanced in cancer cells compared with normal cells. Treatment with MEK inhibitor (U0126) resulted in a reduced MDM2 level, enhanced p53 and p21 levels and inhibited cell growth by the induction of premature senescence. (2) The effect of MEK inhibitor on cell growth was affected by ER levels and functions. Treatment with low-dose MEK inhibitor in combination with anti-estrogen (ICI182,780) had a more inhibitory effect on cell growth compared to treatment with MEK inhibitor or anti-estrogen alone in cancer cells. Down-regulation of the MDM2 level by siRNA resulted in the inhibition of growth in cancer cells.2. We isolated SP cells from the human endometrium and analyzed their properties. SP cells were present in normal human endometrial cells. Most SP cells were enriched in the CD9-CD13- fraction. These SP cells showed long-term repopulating properties and produced gland(CD9 positive)- and stroma(CD13 positive)-like cells. SP cells in the human endometrium can function as progenitor cells. This is the first report of the phenotype of SP cells from normal human endometrial cells.3. We determined the correlation between PR-B expression and cell cycle progression. In synchronized NIH3T3 cells, we found an increase in PR-B protein and p27 CDK inhibitor levels in the G0/G1 phase and a reduction due to redistribution in the S and G2/M phases. The decrease in the PR-B levels caused by anti-sense oligomers or siRNA corresponded to the reduction in p27 levels. PR-B overexpression by adenovirus infection induced p27 and suppressed cell growth. Finally, we showed that induction of PR-B involved in the regulation of NIH3T3 cell proliferation was estrogen(E2)/estrogen receptor (ER) independent.

1.我们先前证明Ras/ER/MDM 2通路对于NIH 3 T3细胞转化是关键的。在这项研究中，我们研究了阻断这一途径对妇科癌细胞生长的影响。(1)与正常细胞相比，癌细胞中的MDM 2水平增强。用MEK抑制剂（U 0126）处理导致MDM 2水平降低，p53和p21水平升高，并通过诱导过早衰老来抑制细胞生长。(2)MEK抑制剂对细胞生长的影响受ER水平和功能的影响。在癌细胞中，与单独使用MEK抑制剂或抗雌激素治疗相比，使用低剂量MEK抑制剂与抗雌激素（ICI 182，780）联合治疗对细胞生长具有更强的抑制作用。通过siRNA下调MDM 2水平导致癌细胞生长的抑制.我们从人子宫内膜分离SP细胞并分析其特性。SP细胞存在于正常人子宫内膜细胞中。大多数SP细胞富集在CD 9-CD 13-组分中。这些SP细胞表现出长期重新繁殖的特性，并产生腺体（CD 9阳性）和基质（CD 13阳性）样细胞。人子宫内膜中的SP细胞可作为祖细胞发挥功能。这是首次报道正常人子宫内膜细胞中SP细胞的表型.我们确定了PR-B表达与细胞周期进程之间的相关性。在同步化的NIH 3 T3细胞中，我们发现PR-B蛋白和p27 CDK抑制剂水平在G 0/G1期增加，而在S和G2/M期由于再分布而减少。由反义寡聚体或siRNA引起的PR-B水平的降低对应于p27水平的降低。PR-B过表达腺病毒感染诱导p27和抑制细胞生长。最后，我们发现PR-B的诱导参与NIH 3 T3细胞增殖的调节是雌激素（E2）/雌激素受体（ER）非依赖性的。

项目成果

ビスフォスフォネート(アセンドロネート)の癌細胞への効果の検討

检查双膦酸盐（ascendronate）对癌细胞的影响

• 发表时间: 2007
• 期刊: Osteoporosis Japan 15
• 作者: 加藤 聖子;他
• 通讯作者: 他

Zac, LIT1(KCNQ10T1) and p57KIP2(CDKN1C) are in an imprinted gene network which may play a role in Beckwith-Wiedemann Syndrome.

Zac、LIT1(KCNQ10T1) 和 p57KIP2(CDKN1C) 位于印记基因网络中，可能在 Beckwith-Wiedemann 综合征中发挥作用。

• 发表时间: 2005
• 期刊: Nucleic Acids Research 33;8
• 作者: Kamikihara;T.;Arima;T.;Kato;K.;Matsuda;T.;Kato;H.;Douchi;T.;Nagata;Y.;Wake;N;Horiuchi S;Kamikihara T;Arima T
• 通讯作者: Arima T

子宮内膜発癌機構におけるstem-like-cellの関与

干细胞样细胞参与子宫内膜癌发生

• 发表时间: 2006
• 作者: 加藤 聖子;他;加藤 聖子
• 通讯作者: 加藤 聖子

HOP/NECC1, a novel regulator of mouse trophoblast differentiation

• DOI: 10.1074/jbc.m701380200
• 发表时间: 2007-08-17
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Asanoma, Kazuo;Kato, Hidenori;Wake, Norio
• 通讯作者: Wake, Norio

エストロゲン依存性腫瘍の発癌機構の解明と治療法の開発

雌激素依赖性肿瘤致癌机制的阐明及治疗方法的开发

• 发表时间: 2005
• 作者: 加藤 聖子;他;加藤 聖子
• 通讯作者: 加藤 聖子