The biological significance of sex-steroid metabolism and responsive genes in the endometrium and breast

子宫内膜和乳腺中性类固醇代谢和反应基因的生物学意义

• 批准号: 17591713
• 负责人: ITO Kiyoshi
• 金额: $ 2.18万
• 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: 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-17591713/
• 关键词: Endometrial cancer; Breast cancer; Progesterone receptor; Estrogen; Cyclin B1; CDC2; Hormone replacement therapy; 癌; 酵素; シグナル伝達; 臨床; 遺伝子

This study aims to investigate whether the biological role of estrogen and progestin in tumorigenesis are different between the endometrium and breast. The possible role of specific progesterone receptor (PR) isoforms (PRA and PRB) as predictive factors in endometrial and breast carcinomas is unclear. This study was undertaken to evaluate the clinical significance of intratumoral PR isoforms status in patients with endometrioid endometrial and breast carcinomas. We found that cases that were negative for either one or both of the PR isoforms were significantly associated with shorter disease-free and overall survival of the patients. In addition, multivariate analysis demonstrated that an absence of PRA immunoreactivity was an independent risk factor in disease-free survival of the patients. The results of our study indicate that the loss of expression of PR isoforms, especially expression of PRA, may result in aggressive biological characteristics in human endometrioid endometrial carcinoma that can play important roles in the prognosis and/or recurrence, in these patients. In contrast, breast carcinoma patients with PRA-rich tumors were generally considered to be associated with poorer disease-free survival rates. These results indicate that the biological significance of PR isoforms differ markedly between endometrial and breast carcinomas.In addition, microarray analyses of human breast and endometrial cancer cells revealed that there are large amount of differences between them, regarding estrogen and progestin responsive gene expression.Especially, cell cycle related genes, cyclin B and CDC, expressed differently between them.These data suggest that the biological roles of estrogen and progestin in tumorigenesis are certainly different between the endometrium and breast, although both are considered "estrogen-dependent tissues".

本研究旨在探讨雌激素和黄体酮在子宫内膜和乳腺肿瘤发生中的生物学作用是否不同。特异性孕激素受体（PR）异构体（PRA和PRB）作为子宫内膜癌和乳腺癌的预测因素的可能作用尚不清楚。本研究旨在评估子宫内膜样子宫内膜癌和乳腺癌患者瘤内PR亚型状态的临床意义。我们发现，一种或两种PR亚型阴性的病例与较短的无病生存期和总生存期显著相关。此外，多变量分析表明，缺乏PRA免疫反应性是患者无病生存的独立危险因素。我们的研究结果表明，PR亚型的表达缺失，特别是PRA的表达缺失，可能导致人类子宫内膜样子宫内膜癌具有侵袭性的生物学特征，对这些患者的预后和/或复发起重要作用。相比之下，富含pra的乳腺癌患者通常被认为与较差的无病生存率相关。这些结果表明PR亚型在子宫内膜癌和乳腺癌中的生物学意义有显著差异。此外，对人乳腺癌和子宫内膜癌细胞的微阵列分析显示，它们在雌激素和黄体酮应答基因表达方面存在很大差异。特别是细胞周期相关基因cyclin B和CDC在它们之间的表达存在差异。这些数据表明，雌激素和黄体酮在子宫内膜和乳房肿瘤发生中的生物学作用肯定是不同的，尽管两者都被认为是“雌激素依赖组织”。

项目成果

Expression of organic cation transporter SLC22A16 in human endometria

• DOI: 10.1097/01.pgp.0000225845.67245.b3
• 发表时间: 2007-01-01
• 期刊: INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY
• 影响因子: 2.4
• 作者: Sato, Naoko;Ito, Kiyoshi;Yaegashi, Nobuo
• 通讯作者: Yaegashi, Nobuo

14-3-3 Sigma in endometrial cancer - a possible prognostic marker m early stage cancer-

14-3-3 子宫内膜癌中的 Sigma - 早期癌症的可能预后标志物 -

• 发表时间: 2005
• 期刊: Clinical Cancer Research 11
• 作者: Ito K;Suzuki T;Akahira J;Sakuma M;Saitou S;Okamoto S;Niikura H;Okamura K;Yaegashi N;Sasano H;Inoue S
• 通讯作者: Inoue S

17β-hydroxy steroid dehydrogenases in human endometrium and its disorders

• DOI: 10.1016/j.mce.2005.11.038
• 发表时间: 2006-03-27
• 期刊: MOLECULAR AND CELLULAR ENDOCRINOLOGY
• 影响因子: 4.1
• 作者: Ito, K;Utsunomiya, H;Sasano, H
• 通讯作者: Sasano, H

Progesterone receptor isoforms as a prognostic marker in human endometrial carcinoma

• DOI: 10.1111/j.1349-7006.2006.00332.x
• 发表时间: 2006-12-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Saito, Sumika;Ito, Kiyoshi;Sasano, Hironobu
• 通讯作者: Sasano, Hironobu

Biosynthesis and action of estrogen in gynecological cancers.

雌激素在妇科癌症中的生物合成和作用。

• 发表时间: 2007
• 期刊: Reproduct Oncol (in press)
• 作者: Kaneko;T.;Sasaki;S.;Umemoto;Y.;Koiima;Y.;Ikeuchi;T.;Kohri;K;Kojima et al.;Kojima et al.;Hayashi S.;Ito K.;Sato N.;Hayashi S.
• 通讯作者: Hayashi S.