Estrogen receptor α controls a gene network in luminal-like breast cancer cells comprising multiple transcription factors and microRNAs
| Autor: | Alessandro Weisz, Ornella Paris, Olì M. V. Grober, Gary P. Schroth, Maria Ravo, Shujun Luo, Michele De Bortoli, Martin Seifert, Luigi Cicatiello, Roberta Tarallo, Lorenzo Ferraro, Christian Zinser, Maria Luisa Chiusano, Alessandra Traini, Margherita Mutarelli |
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| Přispěvatelé: | Cicatiello, L, Mutarelli, M, Grober, Omv, Paris, O, Ferraro, L, Ravo, M, Tarallo, R, Luo, S, Schroth, Gp, Seifert, M, Zinser, C, Chiusano, MARIA LUISA, Traini, A, De Bortoli, M, Weisz, A., Cicatiello, L., Mutarelli, M., Grober, O. M., Paris, O., Ferraro, L., Ravo, M., Tarallo, R., Luo, S., Schroth, G. P., Seifert, M., Zinser, C., Traini, A., De Bortoli, M. |
| Rok vydání: | 2010 |
| Předmět: |
Chromatin Immunoprecipitation
Breast Neoplasms Biology Models Biological Pathology and Forensic Medicine genomic Cell Line Tumor Humans Enhancer Transcription factor Estrogen receptor beta Oligonucleotide Array Sequence Analysis Regulation of gene expression Sp1 transcription factor Binding Sites Estradiol Gene Expression Profiling Liver receptor homolog-1 Estrogen Receptor alpha GATA3 Gene Expression Regulation Neoplastic Kinetics MicroRNAs gene network Cancer research RNA Estrogen receptor alpha Transcription Factors Regular Articles estrogen receptor |
| Popis: | Luminal-like breast tumor cells express estrogen receptor alpha (ERalpha), a member of the nuclear receptor family of ligand-activated transcription factors that controls their proliferation, survival, and functional status. To identify the molecular determinants of this hormone-responsive tumor phenotype, a comprehensive genome-wide analysis was performed in estrogen stimulated MCF-7 and ZR-75.1 cells by integrating time-course mRNA expression profiling with global mapping of genomic ERalpha binding sites by chromatin immunoprecipitation coupled to massively parallel sequencing, microRNA expression profiling, and in silico analysis of transcription units and receptor binding regions identified. All 1270 genes that were found to respond to 17beta-estradiol in both cell lines cluster in 33 highly concordant groups, each of which showed defined kinetics of RNA changes. This hormone-responsive gene set includes several direct targets of ERalpha and is organized in a gene regulation cascade, stemming from ligand-activated receptor and reaching a large number of downstream targets via AP-2gamma, B-cell activating transcription factor, E2F1 and 2, E74-like factor 3, GTF2IRD1, hairy and enhancer of split homologue-1, MYB, SMAD3, RARalpha, and RXRalpha transcription factors. MicroRNAs are also integral components of this gene regulation network because miR-107, miR-424, miR-570, miR-618, and miR-760 are regulated by 17beta-estradiol along with other microRNAs that can target a significant number of transcripts belonging to one or more estrogen-responsive gene clusters. |
| Databáze: | OpenAIRE |
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