Biological characteristics of hormone independent (ER-negative/HER2-negative) breast cancers.

激素非依赖性（ER 阴性/HER2 阴性）乳腺癌的生物学特征。

• 批准号: 15590317
• 负责人: UMEMURA Shinobu
• 金额: $ 2.24万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590317/
• 关键词: breast cancer; ER-negative; HER2-negative; E2F-5; cell proliferation; Ki-67; エストロゲンレセプター; human epidermal growth factor receptor

Purpose : Our goal was to find genes that are differentially expressed in breast cancers lacking estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) and that might significantly contribute to cell proliferation in these cancers.Experimental Design : Forty tumor samples consisting of 10 each of immunohistochemically ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(+), and ER(-)/HER2(-) cancers were analyzed by an oligonucleotide microarray method. Both genes and tumors samples were subjected to hierarchical clustering.Results : In hierarchical clustering, a gene cluster including CK5/6 corresponded to the tumor cluster containing mostly ER(-)/HER2(-) cancers. ER(-)/HER2(-) cancers displayed 55 overexpressed genes and 102 underexpressed genes. Differentially expressed genes included several cell cycle related genes : overexpression of p16, cdc20, and E2F-5 and underexpression of cyclin D1 and CDK7. Ki-67 gene expression was highest in ER(-)/HER2(-) cancers and correlated with expression of cyclins A, B, and E and cdc20 in individual cancers of all four immunohistochemical groups. Interestingly, expression of the transcriptional factor E2F-5 was correlated with Ki-67 in ER(-)/HER2(-) cancers only. Immunohistochemistry revealed E2F-5 in five of ten ER(-)/HER2(-) cancers, with localization in the cytoplasm but not in the nucleus.Conclusions : This is the first report demonstrating overexpression in human breast cancer of E2F-5, a transcription factor with roles in terminal differentiation and in p16/ pocket protein-mediated G1 arrest. This result suggests that E2F-5, whether or not it is functioning normally, has a role in IHC-ER(-)/HER2(-) cancers.

目的：我们的目标是找到在缺乏雌激素受体（ER）和人表皮生长因子受体2（HER 2）的乳腺癌中差异表达的基因，这些基因可能显著促进这些癌症中的细胞增殖。通过寡核苷酸微阵列方法分析40个肿瘤样品，所述肿瘤样品由化学计量的ER（+）/HER 2（-）、ER（+）/HER 2（+）、ER（-）/HER 2（+）和ER（-）/HER 2（-）癌症各10个组成。结果：在系统聚类中，包含CK 5/6的基因簇对应于以ER（-）/HER 2（-）癌为主的肿瘤簇。ER（-）/HER 2（-）癌中有55个基因过表达，102个基因低表达。差异表达的基因包括几个细胞周期相关基因：p16，cdc 20和E2 F-5的过表达和cyclin D1和CDK 7的低表达。Ki-67基因表达在ER（-）/HER 2（-）癌中最高，并且与所有四个免疫组化组的个体癌中细胞周期蛋白A、B、E和cdc 20的表达相关。有趣的是，转录因子E2 F-5的表达仅在ER（-）/HER 2（-）癌症中与Ki-67相关。免疫组化显示E2 F-5在10个ER（-）/HER 2（-）癌中的5个中，定位于细胞质中而不在细胞核中。结论：这是第一份证明E2 F-5在人乳腺癌中过表达的报告，E2 F-5是一种在终末分化和p16/ pocket蛋白介导的G1期阻滞中起作用的转录因子。这一结果表明，E2 F-5，无论其功能是否正常，都在IHC-ER（-）/HER 2（-）癌症中发挥作用。

项目成果

Application of microarray for analysis of tumor characteristics; usefulness and limitation.

应用微阵列分析肿瘤特征；

• 发表时间: 2003
• 期刊: Mod Pathol 16
• 作者: Umemura S;et al.
• 通讯作者: et al.

Umemura S, et al.: "Immunohistochemical evaluation of hormone receptors in breast cancer : Determining which evaluation system is suitable for highly sensitive procedures."Appl Immunohistochem Mol Morphol. (in press).

Umemura S 等人：“乳腺癌激素受体的免疫组织化学评估：确定哪种评估系统适合高度敏感的程序。”ApplImmunohistochem Mol Morphol。

Sekido Y, Umemura S, et al.: "Heterogeneous gene alterations in primary breast cancer contribute to discordance between primary and asynchronous metastatic/recurrent sites : HER2 gene amplification and p53 mutation."Int J Oncol. 22. 1225-1232 (2003)

Sekido Y、Umemura S 等人：“原发性乳腺癌中的异质基因改变导致原发性和异步转移/复发部位之间的不一致：HER2 基因扩增和 p53 突变。”Int J Oncol。

Estrogen receptor-negative and human epidermal growth factor receptor 2-negative breast cancer tissue have the highest Ki-67 lageling index and EGFR expression : Gene amplification does not contribute to EGFR expression.

雌激素受体阴性和人表皮生长因子受体2阴性乳腺癌组织具有最高的Ki-67标记指数和EGFR表达：基因扩增对EGFR表达没有贡献。

• 发表时间: 2005
• 期刊: Oncology Reports 14
• 作者: Umemura S;et al.
• 通讯作者: et al.

Immunohistochemical evaluation of hormone receptors in breast cancer : which scoring system is suitable for highly sensitive procedures?

乳腺癌激素受体的免疫组织化学评估：哪种评分系统适合高度敏感的程序？

• 发表时间: 2004
• 期刊: Appl Immunohistochem Mol Morphol 12
• 作者: Umemura S;Itoh J;Itoh H;Serizawa A;Saitoh Y;Suzuki Y;Tokuda Y;Tajima T;Osamura RY.
• 通讯作者: Osamura RY.