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

被引：52

作者：

Shigekawa T. ^{[1
,2
,4
]}

Ijichi N. ^{[1
]}

Ikeda K. ^{[1
]}

Horie-Inoue K. ^{[1
]}

Shimizu C. ^{[3
]}

Saji S. ^{[4
,5
]}

Aogi K. ^{[7
]}

Tsuda H. ^{[6
]}

Osaki A. ^{[2
]}

Saeki T. ^{[2
]}

Inoue S. ^{[1
,8
,9
]}

机构：

[1] Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama

[2] Department of Breast Oncology, International Medical Center, Saitama Medical University, Saitama

[3] Division of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo

[4] Division of Clinical Trials and Research and Department of Surgery, Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Tokyo

[5] Department of Medical Oncology, International Medical Center-Comprehensive Cancer Center, Saitama Medical University, Saitama

[6] Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo

[7] Department of Surgery, National Shikoku Cancer Center, Ehime

[8] Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo

[9] Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, 7-3-1 Hongo, Bunkyo-ku

来源：

Hormones and Cancer | 2011年 / 2卷 / 5期

基金：

日本学术振兴会;

关键词：

Breast cancer; ERα; Estrogen; FOXP1; Recurrence; Tamoxifen;

D O I：

10.1007/s12672-011-0082-6

中图分类号：

学科分类号：

摘要：

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. © 2011 Springer Science+Business Media, LLC.

引用

页码：286 / 297

页数：11

共 45 条

[1]

Platet N., Cathiard A.M., Gleizes M., Garcia M., Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion, Crit Rev Oncol Hematol, 51, pp. 55-67, (2004)

[2]

Hall J.M., McDonnell D.P., Coregulators in nuclear estrogen receptor action: from concept to therapeutic targeting, Mol Interv, 5, pp. 343-357, (2005)

[3]

Carroll J.S., Brown M., Estrogen receptor target gene: an evolving concept, Mol Endocrinol, 20, pp. 1707-1714, (2006)

[4]

Carroll J.S., Liu X.S., Brodsky A.S., Li W., Meyer C.A., Szary A.J., Eeckhoute J., Shao W., Hestermann E.V., Geistelinger T.R., Fox E.A., Silver P.A., Brown M., Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1, Cell, 122, pp. 33-43, (2005)

[5]

Lupien M., Eeckhoute J., Meyer C.A., Wang Q., Zhang Y., Li W., Carroll J.S., Liu X.S., Brown M., FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription, Cell, 132, pp. 958-970, (2008)

[6]

Grange T., Roux J., Rigaud G., Pictet R., Cell-type specific activity of two glucocorticoid responsive units of rat tyrosine aminotransferase gene is associated with multiple binding sites for C/EBP and a novel liver-specific nuclear factor, Nucleic Acids Res, 19, pp. 131-139, (1991)

[7]

Schuur E.R., Loktev A.V., Sharma M., Sun Z., Roth R.A., Weigel R.J., Ligand-dependent interaction of estrogen receptor-alpha with members of the forkhead transcription factor family, J Biol Chem, 276, pp. 33554-33560, (2001)

[8]

Li S., Weidenfeld J., Morrisey E.E., Transcriptional and DNA binding activity of the Foxp1/2/4 family is modulated by heterotypic and homotypic protein interactions, Mol Cell Biol, 24, pp. 809-822, (2004)

[9]

Wang B., Lin D., Li C., Tucker P., Multiple domains define the expression and regulatory properties of Foxp1 forkhead transcriptional repressors, J Biol Chem, 278, pp. 24259-24268, (2003)

[10]

Banham A.H., Beasley N., Campo E., Fernandez P.L., Fidler C., Gatter K., Jones M., Mason D.Y., Prime J.E., Trougouboff P., Wood K., Cordell J.L., The FOXP1 winged helix transcription factor is a novel candidate tumor suppressor gene on chromosome 3p, Cancer Res, 61, pp. 8820-8829, (2001)

← 1 2 3 4 5 →