Comparative Cistromics Reveals Genomic Cross-talk between FOXA1 and ER alpha in Tamoxifen-Associated Endometrial Carcinomas
| العنوان: | Comparative Cistromics Reveals Genomic Cross-talk between FOXA1 and ER alpha in Tamoxifen-Associated Endometrial Carcinomas |
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| المؤلفون: | Mark Opdam, Sabine C. Linn, Michael Hauptmann, Harry Hollema, Lodewyk F. A. Wessels, Marian J.E. Mourits, Marjolein Droog, Koen D. Flach, Wilbert Zwart, Karianne Schuurman, Tesa M. Severson, Flora E. van Leeuwen, Patrycja Gradowska, Hester van Boven, Yongsoo Kim, Petra M. Nederlof, Gwen M. H. E. Dackus, Ekaterina Nevedomskaya |
| المساهمون: | Targeted Gynaecologic Oncology (TARGON), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Pathology, Epidemiology and Data Science, EMGO - Quality of care |
| المصدر: | Droog, M, Kim, Y, Nevedomskaya, E, Severson, T, Flach, K D, Opdam, M, Schuurman, K, Gradowska, P, Hauptmann, M, Dackus, G, Hollema, H, Mourits, M, Nederlof, P, Van Boven, H, Linn, S C, Wessels, L, Van Leeuwen, F E & Zwart, W 2016, ' Comparative cistromics reveals genomic cross-talk between FOXA1 and ERα in tamoxifen-associated endometrial carcinomas ', Cancer Research, vol. 76, no. 13, pp. 3773-3784 . https://doi.org/10.1158/0008-5472.CAN-14-1813Test Cancer Research, 76(13), 3773-3784. AMER ASSOC CANCER RESEARCH Cancer Research, 76(13), 3773-3784. American Association for Cancer Research Inc. |
| بيانات النشر: | AMER ASSOC CANCER RESEARCH, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Cancer Research, FORKHEAD-BOX A1, Immunoenzyme Techniques, 0302 clinical medicine, PROGNOSTIC-SIGNIFICANCE, TRANSCRIPTION FACTOR, skin and connective tissue diseases, RISK, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Female, ESTROGEN-RECEPTOR-ALPHA, Signal Transduction, medicine.drug, Hepatocyte Nuclear Factor 3-alpha, EXPRESSION, Chromatin Immunoprecipitation, medicine.medical_specialty, Antineoplastic Agents, Hormonal, Breast Neoplasms, Biology, LUMINAL SUBTYPE, Real-Time Polymerase Chain Reaction, Response Elements, CELL-PROLIFERATION, 03 medical and health sciences, Breast cancer, Internal medicine, Biomarkers, Tumor, medicine, Humans, BREAST-CANCER, RNA, Messenger, Transcription factor, Endometrial cancer, Estrogen Receptor alpha, Cancer, medicine.disease, Endometrial Neoplasms, Tamoxifen, 030104 developmental biology, Cancer research, FOXM1, FOXA1, Estrogen receptor alpha, RESISTANCE |
| الوصف: | Tamoxifen, a small-molecule antagonist of the transcription factor estrogen receptor alpha (ERα) used to treat breast cancer, increases risks of endometrial cancer. However, no parallels of ERα transcriptional action in breast and endometrial tumors have been found that might explain this effect. In this study, we addressed this issue with a genome-wide assessment of ERα-chromatin interactions in surgical specimens obtained from patients with tamoxifen-associated endometrial cancer. ERα was found at active enhancers in endometrial cancer cells as marked by the presence of RNA polymerase II and the histone marker H3K27Ac. These ERα binding sites were highly conserved between breast and endometrial cancer and enriched in binding motifs for the transcription factor FOXA1, which displayed substantial overlap with ERα binding sites proximal to genes involved in classical ERα target genes. Multifactorial ChIP-seq data integration from the endometrial cancer cell line Ishikawa illustrated a functional genomic network involving ERα and FOXA1 together with the enhancer-enriched transcriptional regulators p300, FOXM1, TEAD4, FNFIC, CEBP8, and TCF12. Immunohistochemical analysis of 230 primary endometrial tumor specimens showed that lack of FOXA1 and ERα expression was associated with a longer interval between breast cancer and the emergence of endometrial cancer, exclusively in tamoxifen-treated patients. Our results define conserved sites for a genomic interplay between FOXA1 and ERα in breast cancer and tamoxifen-associated endometrial cancer. In addition, FOXA1 and ERα are associated with the interval time between breast cancer and endometrial cancer only in tamoxifen-treated breast cancer patients. Cancer Res; 76(13); 3773–84. ©2016 AACR. |
| اللغة: | English |
| تدمد: | 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::36c889c8917664f080399220df564bdaTest https://research.rug.nl/en/publications/23754f80-627e-40bc-a802-317a2a8d331fTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....36c889c8917664f080399220df564bda |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00085472 |
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