Slug contributes to cancer progression by direct regulation of ERα signaling pathway
| العنوان: | Slug contributes to cancer progression by direct regulation of ERα signaling pathway |
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| المؤلفون: | Suren Sarkissyan, Seyung S. Chung, Jaydutt V. Vadgama, Ju Ri Kim, Yahya Elshimali, Youqiang Li, Yanyuan Wu, Warren L. Wu, Thomas C. Abbatiello, Marianna Sarkissyan |
| المصدر: | International Journal of Oncology |
| بيانات النشر: | Spandidos Publications, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, Cancer Research, medicine.medical_specialty, animal structures, Slug, Mice, Nude, Estrogen receptor, Breast Neoplasms, Mice, breast cancer, Cell Line, Tumor, Internal medicine, medicine, Animals, Humans, DNA binding, Transcription factor, ERα, biology, fungi, Estrogen Receptor alpha, Mammary Neoplasms, Experimental, Prostatic Neoplasms, Cancer, Articles, Cell cycle, prostate cancer, medicine.disease, biology.organism_classification, 3. Good health, Tamoxifen, Endocrinology, Oncology, Drug Resistance, Neoplasm, Tumor progression, embryonic structures, Cancer cell, Disease Progression, MCF-7 Cells, Cancer research, Female, Snail Family Transcription Factors, Estrogen receptor alpha, Signal Transduction, Transcription Factors |
| الوصف: | Hormone therapy targeting estrogen receptor α (ERα) is the most effective treatment for breast cancer. However, this treatment eventually fails as the tumor develops resistance. Although reduced expression of ER-α is a known contributing factor to endocrine resistance, the mechanism of ER-α downregulation in endocrine resistance is still not fully understood. The present study shows that Slug has an inverse relationship with ERα in breast and prostate cancer patient samples. Also the inhibition of Slug blocks mammary stem cell activity in primary mammary epithelial cells. We hypothesize that Slug may be a key transcription factor in the regulation of ERα expression. To understand the Slug-ERα signaling pathway, we employed resistant cell line MCF-TAMR (ERα relatively negative) derived from its parental MCF-7 (ERα positive) cell line and assessed changes in cell phenotype, activity and response to therapy. Conversely, we performed knockdown of Slug in the high-Slug expressing cell line MDA-MB-231 and assessed reversal of the mesenchymal phenotype. Microarray analysis showed that Slug is overexpressed in high grade breast and prostate cancer tissues. Additionally, Slug overexpression leads to drug resistance. Furthermore, we demonstrated that Slug binds directly to ERα promoter E-boxes and represses ERα expression. This resulted in decrease in epithelial-to-mesenchymal transition in cancer cells. These findings demonstrate that Slug, by regulation of ERα expression, contributes to tumor progression and could serve as an important target for cancer therapy. |
| تدمد: | 1791-2423 1019-6439 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d601b7306e5766dbde5f7f03d0436c13Test https://doi.org/10.3892/ijo.2015.2878Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d601b7306e5766dbde5f7f03d0436c13 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17912423 10196439 |
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