Investigation of in situ estrogen metabolism and estrogen responsive gene in endometrial cancer : New aspects of hormone therapy

子宫内膜癌原位雌激素代谢和雌激素反应基因的研究：激素治疗的新方面

• 批准号: 14571533
• 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: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571533/
• 关键词: estrogen; 17βHSD2; endometrial cancer; androaen; hormone therapy; estrogen responsive gene; steroid sulfatase; estrogen sulfotransferase; 大規模遺伝子解析; エストロゲン応答遺伝子; ホルモンレセプター関連遺伝子; 正常子宮内膜; アロマターゼ; ホルモン濃度; 17beta-hydroxysteroide dehydrogenase

In situ estrogen metabolism and synthesis have been considered to play a very important role in the development and progression of human endometrial carcinomas. The correlation between tissue concentrations of estrogens and status of intratumoral enzymes has, however, not been examined in endometrial carcinoma. Therefore, in this study, we examined the concentrations of estrone (E1), estradiol (E2), and testosterone in carcinoma tissue and plasma as well as intratumoral enzymes activities in carcinoma tissues of postmenopausal patients with endometrial carcinoma. The concentrations of E1, E2 and testosterone in endometrial cancer tissue were significantly higher than those in serum. Various types of intratumorall enzymes expression which included 17 β-hydroxysteroid dehydrogenase type 2 (17 β-HSD type 2), 17 β-HSD type 5, steroid sulfatase, estrogen sulfotransferase and aromatase, were observed in endometrial carcinoma. There was a statistically significant inverse correlation between intratumoral estradiol concentration and the level of 17 β-HSD type 2 mRNA. A statistically significant inverse correlation was detected between tumor tissue testosterone and aromatase mRNA expression level. These results suggest that several intratumoral enzymes expression, especially 17 β-HSD type 2 and aromatase, contribute to intratumoral estrogen levels in human endometrial carcinoma. Moreover, our results suggested that in situ abundance of 17 β-HSD type 2 can predict the possible response of patients with endometrial carcinoma to progestogen treatment. In summary, Estrogen biosynthesis pathway in endometrial cancers is quite different from that in breast cancers. Using cDNA microarrays, I investigated estrogen responsive gene expression in breast and endometrial cancer cell lines. I also suggest that there are large amount of differences between breast and endometrial cancers, regarding estrogen responsive gene expression, which are associated with various actions.

原位雌激素代谢和合成在子宫内膜癌的发生发展中起着重要作用。然而，在子宫内膜癌中，雌激素的组织浓度和肿瘤内酶的状态之间的相关性尚未得到研究。因此，在这项研究中，我们研究了雌酮（E1），雌二醇（E2），睾酮在癌组织和血浆中的浓度，以及在癌组织中的酶活性绝经后子宫内膜癌患者。子宫内膜癌组织中E1、E2和睾酮浓度均显著高于血清。17 β-羟类固醇脱氢酶2型（17 β-HSD 2型）、17 β-HSD 5型、类固醇硫酸酯酶、雌激素磺基转移酶和芳香化酶在子宫内膜癌中均有表达。肿瘤内雌二醇浓度与17 β-HSD 2型mRNA水平呈显著负相关。肿瘤组织睾酮水平与芳香化酶mRNA表达水平呈显著负相关。这些结果表明，一些肿瘤内酶的表达，特别是17 β-HSD 2型和芳香化酶，有助于在人子宫内膜癌肿瘤内雌激素水平。此外，我们的研究结果表明，原位丰度的17 β-HSD 2型可以预测子宫内膜癌患者对孕激素治疗的可能反应。综上所述，子宫内膜癌雌激素生物合成途径与乳腺癌有很大不同。使用cDNA微阵列，我研究了乳腺癌和子宫内膜癌细胞系中雌激素反应基因的表达。我还认为乳腺癌和子宫内膜癌之间在雌激素反应基因表达方面存在大量差异，这些差异与各种行为有关。

项目成果

E4F1, a novel estrogen-responsive gene in possible atheroprotection, revealed by microarray analysis.

• DOI: 10.1016/s0002-9440(10)63253-1
• 发表时间: 2004-12
• 期刊: The American journal of pathology
• 作者: Yasuhiro Nakamura;K. Igarashi;Takashi Suzuki;J. Kanno;Tohru Inoue;C. Tazawa;M. Saruta;T. Ando;N. Moriyama;T. Furukawa;M. Ono;T. Moriya;K. Ito;H. Saito;T. Ishibashi;Shoki Takahashi;S. Yamada;H. Sasano

Steroid sulfatase and estrogen sulfotransferase in human endometrial carcinoma

人子宫内膜癌中的类固醇硫酸酯酶和雌激素磺基转移酶

• 发表时间: 2004
• 期刊: Clin Cancer Res. 10(17)
• 作者: Utsunomiya H;Ito K et al.
• 通讯作者: Ito K et al.

子宮内膜癌における内分泌療法の新たな展開

子宫内膜癌内分泌治疗新进展

• 发表时间: 2005
• 期刊: Medical Science Digest 31(2)
• 作者: 伊藤 潔

Ito.K., Suzuki T., Akahira, J., Moriya T., Kaneko C.Utsunomiya H., Yaegashi N., Okamuru K., Sasano H.: "Expression of androgen receptor and 5 α-reductases in the human normal endometrium and its disorders"Int.J.Cancer.. 99. 652-657 (2002)

Ito.K.、Suzuki T.、Akahira, J.、Moriya T.、Kaneko C.Utsunomiya H.、Yaegashi N.、Okamuru K.、Sasano H.：“雄激素受体和 5 种 α-还原酶在人类中的表达正常子宫内膜及其疾病”Int.J.Cancer.. 99. 652-657 (2002)

New aspects of intracrinology in endometrial cancer ; differences between endometrial and breast cancer

子宫内膜癌分泌内学的新方面；

• 发表时间: 2003
• 期刊: 21(4)
• 作者: 笹野公伸;Utsunomiya H.;Sasano H
• 通讯作者: Sasano H