Identificationof novel diagnostic and therapeutic factors for endocrine therapy-resistant breast cancer by next-generation sequencing strategy

通过下一代测序策略鉴定内分泌治疗耐药乳腺癌的新诊断和治疗因素

• 批准号: 24701033
• 负责人: IJICHI Nobuhiro
• 金额: $ 2.91万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24701033/
• 关键词: 内分泌療法; 乳がん; エストロゲン; FOXP1; 次世代シーケンサー; FOXA1; Erα; タモキシフェン耐性

To identify the novel diagnostic and therapeutic factors for endocrine therapy-resistant breast cancer, we focused on FOXP1, one of a forkhead transcription factor family, as a candidate, and its genome-wide distributionin ERα-positive breast cancer MCF-7 cells was examined by next-generation sequencing strategy. We demonstrated that majority of binding regions of FOXP1 in MCF-7 cells stimulated with estrogen were overlapped with those of both Erαand FOXA1. We also demonstrated that the double-positive immunoreactivities of FOXP1 and FOXA1 are significantly associated with a favorable prognosis for survival of breast cancer patients receiving adjuvant tamoxifen therapy. In this study, we revealed that, similar to FOXA1, FOXP1 is assumed to be a critical transcription factor for Erαsignaling, and both forkhead transcription factors can serve as predictive factors for acquired endocrine resistance in breast cancer.

为了确定内分泌治疗耐药性乳腺癌的新诊断和治疗因子，我们将叉头转录因子家族之一的 FOXP1 作为候选因子，并检查了其在 ERα 阳性乳腺癌 MCF-7 细胞中的全基因组分布。通过下一代测序策略，我们证明了雌激素刺激的 MCF-7 细胞中 FOXP1 的大部分结合区域与 Erα 和 FOXA1 的结合区域重叠。 FOXP1 和 FOXA1 的表达与接受他莫昔芬辅助治疗的乳腺癌患者的良好预后显着相关。在这项研究中，我们发现，与 FOXA1 类似，FOXP1 被认为是 Erα 信号传导和叉头转录的关键转录因子。因素可以作为乳腺癌获得性内分泌抵抗的预测因素。

项目成果

HORMONES AND BREAST CANCER, Elsevier

激素与乳腺癌，爱思唯尔

• 作者: Ijichi N;Ikeda K;Horie-Inoue K;Inoue S
• 通讯作者: Inoue S

フォークヘッド転写因子FOXP1の全ゲノムにおける結合部位同定によるERシグナル調節機構の解析

通过鉴定叉头转录因子FOXP1在全基因组中的结合位点分析ER信号调控机制

• 发表时间: 2012
• 作者: 前田士郎;鎌谷直之;栗原 勲;伊地知暢広
• 通讯作者: 伊地知暢広

ホルモン療法抵抗性前立腺がん細胞におけるエネルギー代謝関連核内受容体作用の検討

检查激素治疗耐药性前列腺癌细胞中与能量代谢相关的核受体效应

• 发表时间: 2012
• 作者: 堀江公仁子;高山賢一;伊地知暢宏;池田和博;井上聡
• 通讯作者: 井上聡

Association of Double-Positive FOXA1 and FOXP1 Immunoreactivities with Favorable Prognosis of Tamoxifen-Treated Breast Cancer Patients

• DOI: 10.1007/s12672-012-0111-0
• 发表时间: 2012-08-01
• 期刊: HORMONES & CANCER
• 影响因子: 3
• 作者: Ijichi, Nobuhiro;Shigekawa, Takashi;Inoue, Satoshi
• 通讯作者: Inoue, Satoshi

Forkhead box transcription factor, forkhead box A1, shows negative association with lymph node status in endometrial cancer, and represses cell proliferation and migration of endometrial cancer cells

• DOI: 10.1111/j.1349-7006.2012.02201.x
• 发表时间: 2012-04-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Abe, Yayoi;Ijichi, Nobuhiro;Inoue, Satoshi
• 通讯作者: Inoue, Satoshi