GREB1 isoforms regulate proliferation independent of ERα co-regulator activities in breast cancer
| العنوان: | GREB1 isoforms regulate proliferation independent of ERα co-regulator activities in breast cancer |
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| المؤلفون: | Kara M. Braunreiter, Xiaokui M Mo, Corinne N Haines, Craig J. Burd |
| المصدر: | Endocrine-Related Cancer. 25:735-746 |
| بيانات النشر: | Bioscientifica, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Gene isoform, Cancer Research, Endocrinology, Diabetes and Metabolism, Estrogen receptor, Breast Neoplasms, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Cell Line, Tumor, Gene expression, Transcriptional regulation, Humans, Protein Isoforms, Transcription factor, Cell Proliferation, Regulation of gene expression, Estrogen Receptor alpha, Neoplasm Proteins, Cell biology, GREB1, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, GREB1 Gene, Female |
| الوصف: | Activation of the transcription factor estrogen receptor α (ERα) and the subsequent regulation of estrogen-responsive genes play a crucial role in the development and progression of the majority of breast cancers. One gene target of ERα, growth regulation by estrogen in breast cancer 1 (GREB1), is associated with proliferation and regulation of ERα activity in estrogen-responsive breast cancer cells. The GREB1 gene encodes three distinct isoforms: GREB1a, GREB1b and GREB1c, whose molecular functions are largely unknown. Here, we investigate the role of these isoforms in regulation of ERα activity and proliferation. Interaction between GREB1 and ERα was mapped to the amino terminus shared by all GREB1 variants. Analysis of isoform-specific regulation of ERα activity suggests none of the GREB1 isoforms possess potent co-regulator activity. Exogenous expression of GREB1a resulted in elevated expression of some ER-target genes, independent of ERα activity. Despite this slight specificity of GREB1a for gene regulation, exogenous expression of either GREB1a or GREB1b resulted in decreased proliferation in both ER-positive and ER-negative breast carcinoma cell lines, demonstrating an ER-independent function of GREB1. Interestingly, we show an increase in the expression of GREB1b and GREB1c mRNA in malignant breast tissue compared to normal patient samples, suggesting a selective preference for these isoforms during malignant transformation. Together, these data suggest GREB1a has an isoform-specific function as a transcriptional regulator while all isoforms share an ER-independent activity that regulates proliferation. |
| تدمد: | 1479-6821 1351-0088 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::addabfc0b275b5238749bfc81f0f5912 https://doi.org/10.1530/erc-17-0496 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....addabfc0b275b5238749bfc81f0f5912 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14796821 13510088 |
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