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TGF-β1 induces HMGA1 expression in human breast cancer cells: Implications of the involvement of HMGA1 in TGF-β signaling
Transforming growth factor-β1 (TGF-β1) signaling and high mobility group A (HMGA1) are known to play essential roles in the progression of breast cancer by inducing epithelial-mesenchymal transition. However, the correlation between TGF-β1 and HMGA1 in breast cancer cell is not yet well understood....
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314408/ https://www.ncbi.nlm.nih.gov/pubmed/25572132 http://dx.doi.org/10.3892/ijmm.2015.2062 |
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author | ZU, XUYU ZHONG, JING TAN, JINGJING TAN, LI YANG, DONG ZHANG, QINGHAI DING, WENJUN LIU, WEN WEN, GEBO LIU, JIANGHUA CAO, RENXIAN JIANG, YUYANG |
author_facet | ZU, XUYU ZHONG, JING TAN, JINGJING TAN, LI YANG, DONG ZHANG, QINGHAI DING, WENJUN LIU, WEN WEN, GEBO LIU, JIANGHUA CAO, RENXIAN JIANG, YUYANG |
author_sort | ZU, XUYU |
collection | PubMed |
description | Transforming growth factor-β1 (TGF-β1) signaling and high mobility group A (HMGA1) are known to play essential roles in the progression of breast cancer by inducing epithelial-mesenchymal transition. However, the correlation between TGF-β1 and HMGA1 in breast cancer cell is not yet well understood. In this study, we determined the effects of TGF-β1 on HMGA1 expression in breast cancer cells and examined the role of HMGA1 in breast cancer progression. Our results demonstrated that TGF-β1 induced the expression of HMGA1 in both MCF-7 and MDA-MB-231 breast cancer cells, as shown by RT-qPCR and immunofluorescence staining; however, the TGF-β1-induced expression of HMGA was blocked by treatment of the cells with phosphatidylinositol-3 kinase (PI3K) signaling inhibitors. Moreover, the HMGA1 promoter activity was found to be activated by TGF-β1 in the MCF-7 and MDA-MB-231 cells and we found that specificity protein 1 (Sp1) was involved in the TGF-β1-induced HMGA1 promoter activity, as shown by luciferase activity assay. Furthermore, the enforced expression of HMGA1 by transfection with a HMGA1 promoter enhanced cellular oncogenic properties, including proliferation, migration and invasion, and a tissue microarray revealed that breast tumors expressing human epidermal growth factor receptor 2 (HER2) showed higher expression levels of HMGA1 (P=0.007). In addition, higher HMGA1 expression levels were also observed in the ductal breast cancer cases compared with the lobular breast cancer cases (P=0.000). These findings establish the first link between HMGA1 and TGF-β1 in breast cancer, providing further evidence of the pivotal role of HMGA1 in breast cancer progression. |
format | Online Article Text |
id | pubmed-4314408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-43144082015-02-06 TGF-β1 induces HMGA1 expression in human breast cancer cells: Implications of the involvement of HMGA1 in TGF-β signaling ZU, XUYU ZHONG, JING TAN, JINGJING TAN, LI YANG, DONG ZHANG, QINGHAI DING, WENJUN LIU, WEN WEN, GEBO LIU, JIANGHUA CAO, RENXIAN JIANG, YUYANG Int J Mol Med Articles Transforming growth factor-β1 (TGF-β1) signaling and high mobility group A (HMGA1) are known to play essential roles in the progression of breast cancer by inducing epithelial-mesenchymal transition. However, the correlation between TGF-β1 and HMGA1 in breast cancer cell is not yet well understood. In this study, we determined the effects of TGF-β1 on HMGA1 expression in breast cancer cells and examined the role of HMGA1 in breast cancer progression. Our results demonstrated that TGF-β1 induced the expression of HMGA1 in both MCF-7 and MDA-MB-231 breast cancer cells, as shown by RT-qPCR and immunofluorescence staining; however, the TGF-β1-induced expression of HMGA was blocked by treatment of the cells with phosphatidylinositol-3 kinase (PI3K) signaling inhibitors. Moreover, the HMGA1 promoter activity was found to be activated by TGF-β1 in the MCF-7 and MDA-MB-231 cells and we found that specificity protein 1 (Sp1) was involved in the TGF-β1-induced HMGA1 promoter activity, as shown by luciferase activity assay. Furthermore, the enforced expression of HMGA1 by transfection with a HMGA1 promoter enhanced cellular oncogenic properties, including proliferation, migration and invasion, and a tissue microarray revealed that breast tumors expressing human epidermal growth factor receptor 2 (HER2) showed higher expression levels of HMGA1 (P=0.007). In addition, higher HMGA1 expression levels were also observed in the ductal breast cancer cases compared with the lobular breast cancer cases (P=0.000). These findings establish the first link between HMGA1 and TGF-β1 in breast cancer, providing further evidence of the pivotal role of HMGA1 in breast cancer progression. D.A. Spandidos 2015-03 2015-01-05 /pmc/articles/PMC4314408/ /pubmed/25572132 http://dx.doi.org/10.3892/ijmm.2015.2062 Text en Copyright © 2015, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Articles ZU, XUYU ZHONG, JING TAN, JINGJING TAN, LI YANG, DONG ZHANG, QINGHAI DING, WENJUN LIU, WEN WEN, GEBO LIU, JIANGHUA CAO, RENXIAN JIANG, YUYANG TGF-β1 induces HMGA1 expression in human breast cancer cells: Implications of the involvement of HMGA1 in TGF-β signaling |
title | TGF-β1 induces HMGA1 expression in human breast cancer cells: Implications of the involvement of HMGA1 in TGF-β signaling |
title_full | TGF-β1 induces HMGA1 expression in human breast cancer cells: Implications of the involvement of HMGA1 in TGF-β signaling |
title_fullStr | TGF-β1 induces HMGA1 expression in human breast cancer cells: Implications of the involvement of HMGA1 in TGF-β signaling |
title_full_unstemmed | TGF-β1 induces HMGA1 expression in human breast cancer cells: Implications of the involvement of HMGA1 in TGF-β signaling |
title_short | TGF-β1 induces HMGA1 expression in human breast cancer cells: Implications of the involvement of HMGA1 in TGF-β signaling |
title_sort | tgf-β1 induces hmga1 expression in human breast cancer cells: implications of the involvement of hmga1 in tgf-β signaling |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314408/ https://www.ncbi.nlm.nih.gov/pubmed/25572132 http://dx.doi.org/10.3892/ijmm.2015.2062 |
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