FOXP1, an Estrogen-Inducible Transcription Factor, Modulates Cell Proliferation in Breast Cancer Cells and 5-Year Recurrence-Free Survival of Patients with Tamoxifen-Treated Breast Cancer

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• 作者：Takashi Shigekawa (1) (2) (4)
  Nobuhiro Ijichi (1)
  Kazuhiro Ikeda (1)
  Kuniko Horie-Inoue (1)
  Chikako Shimizu (3)
  Shigehira Saji (4) (5)
  Kenjiro Aogi (7)
  Hitoshi Tsuda (6)
  Akihiko Osaki (2)
  Toshiaki Saeki (2)
  Satoshi Inoue (1) (8) (9)
  
• 关键词：FOXP1 ; Estrogen ; ERα ; Breast cancer ; Tamoxifen ; Recurrence
• 刊名：Hormones and Cancer
• 出版年：2011
• 出版时间：October 2011
• 年：2011
• 卷：2
• 期：5
• 页码：286-297
• 全文大小：490KB
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• 作者单位：Takashi Shigekawa (1) (2) (4)
  Nobuhiro Ijichi (1)
  Kazuhiro Ikeda (1)
  Kuniko Horie-Inoue (1)
  Chikako Shimizu (3)
  Shigehira Saji (4) (5)
  Kenjiro Aogi (7)
  Hitoshi Tsuda (6)
  Akihiko Osaki (2)
  Toshiaki Saeki (2)
  Satoshi Inoue (1) (8) (9)
  
  1. Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan
  2. Department of Breast Oncology, International Medical Center, Saitama Medical University, Saitama, Japan
  4. Division of Clinical Trials and Research and Department of Surgery, Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Tokyo, Japan
  3. Division of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
  5. Department of Medical Oncology, International Medical Center-Comprehensive Cancer Center, Saitama Medical University, Saitama, Japan
  7. Department of Surgery, National Shikoku Cancer Center, Ehime, Japan
  6. Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan
  8. Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  9. Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
  

文摘

Breast cancer is primarily a hormone-dependent tumor that can be regulated by the status of steroid hormones, including estrogen and progesterone. Forkhead box P1 (FOXP1) is a member of the forkhead box transcription factor family and has been reported to be associated with various types of tumors. In the present study, we investigated the expression of FOXP1 in 133 human invasive breast cancers, obtained by core biopsy, by immunohistochemical analysis. Nuclear immunoreactivity of FOXP1 was detected in 89 cases (67%) and correlated positively with tumor grade and hormone receptor status, including estrogen receptor alpha (ERα) and progesterone receptor, and negatively with pathological tumor size. In ERα-positive MCF-7 breast cancer cells, we demonstrated that FOXP1 mRNA was upregulated by estrogen and increased ERα recruitment to ER binding sites identified by ChIP-on-chip analysis within the FOXP1 gene region. We also demonstrated that proliferation of MCF-7 cells was increased by exogenously transfected FOXP1 and decreased by FOXP1-specific siRNA. Furthermore, FOXP1 enhanced estrogen response element-driven transcription in MCF-7 cells. Finally, FOXP1 immunoreactivity was significantly elevated in relapse-free breast cancer patients treated with tamoxifen. These results suggest that FOXP1 plays an important role in proliferation of breast cancer cells by modulating estrogen signaling and that FOXP1 immunoreactivity could be associated with the estrogen dependency of clinical breast cancers, which may predict favorable prognosis in the patients treated with tamoxifen.