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IL-6 Impairs the Activity of Vitamin D(3) in the Regulation of Epithelial-Mesenchymal Transition in Triple Negative Breast Cancer
OBJECTIVE: The present study aimed to investigate the possible role of IL-6 and 1α,25-dihydroxyvitamin D3 (1,25D) signaling in epithelial-mesenchymal transition (EMT) and stemness in triple-negative breast cancer (TNBC) cell line. METHODS: TNBC cell line, HCC 1806, was treated with IL-6 and 1,25D fo...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
West Asia Organization for Cancer Prevention
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852800/ https://www.ncbi.nlm.nih.gov/pubmed/31450894 http://dx.doi.org/10.31557/APJCP.2019.20.8.2267 |
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author | Abdel-Mohsen, Mohamed A. Abo-Deif, Samar. M Abou-Shamaa, Lobna A. |
author_facet | Abdel-Mohsen, Mohamed A. Abo-Deif, Samar. M Abou-Shamaa, Lobna A. |
author_sort | Abdel-Mohsen, Mohamed A. |
collection | PubMed |
description | OBJECTIVE: The present study aimed to investigate the possible role of IL-6 and 1α,25-dihydroxyvitamin D3 (1,25D) signaling in epithelial-mesenchymal transition (EMT) and stemness in triple-negative breast cancer (TNBC) cell line. METHODS: TNBC cell line, HCC 1806, was treated with IL-6 and 1,25D for three and six days. Also, the role of vitamin D receptor (VDR) was studied by transfection of TNBC cell line with VDR gene and transfection efficiency was assessed using Human VDR enzyme-linked immunosorbent assay (ELISA). Changes in E-cadherin gene expression were analyzed by quantitative real-time PCR (qRT-PCR). Also, changes in CD44+ cells were analyzed by flow cytometry. Finally, morphological changes were investigated by light microscopy after 6 days. RESULTS: Treatment of HCC1806 cells with IL-6 has no significant effect either on E-cadherin gene expression or CD44+ cells, (p > 0.05). However, E-cadherin gene expression was significantly up-regulated after treatment with 1,25D for 6 days, (p < 0.05). Also, CD44+ cells were significantly reduced after treatment with 1,25D either for 3 or 6 days, (p < 0.05). Transfection of TNBC cell line with VDR gene significantly up-regulated VDR protein expression, (p < 0.05). In addition, overexpression of VDR in TNBC cells and treatment with 1,25D significantly up-regulated E-cadherin gene expression, (p < 0.05) and reduced CD44+ cells, (p < 0.05). Moreover, transfection with VDR and treatment with a combination of 1,25D and IL-6 significantly down-regulated E-cadherin gene expression and increased CD44+ cells compared with transfected cells with VDR treated with 1,25D alone, (p < 0.05). No significant morphological changes were observed in treated cells, 6 days post-treatment. CONCLUSION: The presence of IL-6 in the breast tumor microenvironment may impair the activity of vitamin D3 signaling, limiting its anti-tumor effects in TNBC. |
format | Online Article Text |
id | pubmed-6852800 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | West Asia Organization for Cancer Prevention |
record_format | MEDLINE/PubMed |
spelling | pubmed-68528002019-12-12 IL-6 Impairs the Activity of Vitamin D(3) in the Regulation of Epithelial-Mesenchymal Transition in Triple Negative Breast Cancer Abdel-Mohsen, Mohamed A. Abo-Deif, Samar. M Abou-Shamaa, Lobna A. Asian Pac J Cancer Prev Research Article OBJECTIVE: The present study aimed to investigate the possible role of IL-6 and 1α,25-dihydroxyvitamin D3 (1,25D) signaling in epithelial-mesenchymal transition (EMT) and stemness in triple-negative breast cancer (TNBC) cell line. METHODS: TNBC cell line, HCC 1806, was treated with IL-6 and 1,25D for three and six days. Also, the role of vitamin D receptor (VDR) was studied by transfection of TNBC cell line with VDR gene and transfection efficiency was assessed using Human VDR enzyme-linked immunosorbent assay (ELISA). Changes in E-cadherin gene expression were analyzed by quantitative real-time PCR (qRT-PCR). Also, changes in CD44+ cells were analyzed by flow cytometry. Finally, morphological changes were investigated by light microscopy after 6 days. RESULTS: Treatment of HCC1806 cells with IL-6 has no significant effect either on E-cadherin gene expression or CD44+ cells, (p > 0.05). However, E-cadherin gene expression was significantly up-regulated after treatment with 1,25D for 6 days, (p < 0.05). Also, CD44+ cells were significantly reduced after treatment with 1,25D either for 3 or 6 days, (p < 0.05). Transfection of TNBC cell line with VDR gene significantly up-regulated VDR protein expression, (p < 0.05). In addition, overexpression of VDR in TNBC cells and treatment with 1,25D significantly up-regulated E-cadherin gene expression, (p < 0.05) and reduced CD44+ cells, (p < 0.05). Moreover, transfection with VDR and treatment with a combination of 1,25D and IL-6 significantly down-regulated E-cadherin gene expression and increased CD44+ cells compared with transfected cells with VDR treated with 1,25D alone, (p < 0.05). No significant morphological changes were observed in treated cells, 6 days post-treatment. CONCLUSION: The presence of IL-6 in the breast tumor microenvironment may impair the activity of vitamin D3 signaling, limiting its anti-tumor effects in TNBC. West Asia Organization for Cancer Prevention 2019 /pmc/articles/PMC6852800/ /pubmed/31450894 http://dx.doi.org/10.31557/APJCP.2019.20.8.2267 Text en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/) |
spellingShingle | Research Article Abdel-Mohsen, Mohamed A. Abo-Deif, Samar. M Abou-Shamaa, Lobna A. IL-6 Impairs the Activity of Vitamin D(3) in the Regulation of Epithelial-Mesenchymal Transition in Triple Negative Breast Cancer |
title | IL-6 Impairs the Activity of Vitamin D(3) in the Regulation of Epithelial-Mesenchymal Transition in Triple Negative Breast Cancer |
title_full | IL-6 Impairs the Activity of Vitamin D(3) in the Regulation of Epithelial-Mesenchymal Transition in Triple Negative Breast Cancer |
title_fullStr | IL-6 Impairs the Activity of Vitamin D(3) in the Regulation of Epithelial-Mesenchymal Transition in Triple Negative Breast Cancer |
title_full_unstemmed | IL-6 Impairs the Activity of Vitamin D(3) in the Regulation of Epithelial-Mesenchymal Transition in Triple Negative Breast Cancer |
title_short | IL-6 Impairs the Activity of Vitamin D(3) in the Regulation of Epithelial-Mesenchymal Transition in Triple Negative Breast Cancer |
title_sort | il-6 impairs the activity of vitamin d(3) in the regulation of epithelial-mesenchymal transition in triple negative breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852800/ https://www.ncbi.nlm.nih.gov/pubmed/31450894 http://dx.doi.org/10.31557/APJCP.2019.20.8.2267 |
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