Cargando…
Anti-apoptotic role of HIF-1 and AP-1 in paclitaxel exposed breast cancer cells under hypoxia
BACKGROUND: Hypoxia is a hallmark of solid tumors and is associated with metastases, therapeutic resistance and poor patient survival. RESULTS: In this study, we showed that hypoxia protected MDA-MB-231 breast cancer cells against paclitaxel- but not epirubicin-induced apoptosis. The possible implic...
Autores principales: | , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098009/ https://www.ncbi.nlm.nih.gov/pubmed/20626868 http://dx.doi.org/10.1186/1476-4598-9-191 |
_version_ | 1782203904112459776 |
---|---|
author | Flamant, Lionel Notte, Annick Ninane, Noelle Raes, Martine Michiels, Carine |
author_facet | Flamant, Lionel Notte, Annick Ninane, Noelle Raes, Martine Michiels, Carine |
author_sort | Flamant, Lionel |
collection | PubMed |
description | BACKGROUND: Hypoxia is a hallmark of solid tumors and is associated with metastases, therapeutic resistance and poor patient survival. RESULTS: In this study, we showed that hypoxia protected MDA-MB-231 breast cancer cells against paclitaxel- but not epirubicin-induced apoptosis. The possible implication of HIF-1 and AP-1 in the hypoxia-induced anti-apoptotic pathway was investigated by the use of specific siRNA. Specific inhibition of the expression of these two transcription factors was shown to increase apoptosis induced by chemotherapeutic agents under hypoxia indicating an involvement of HIF-1 and AP-1 in the anti-apoptotic effect of hypoxia. After HIF-1 specific inhibition and using TaqMan Human Apoptosis Array, 8 potential HIF-1 target genes were identified which could take part in this protection. Furthermore, Mcl-1 was shown to be a potential AP-1 target gene which could also participate to the hypoxia-induced chemoresistance. CONCLUSIONS: Altogether, these data highlight two mechanisms by which hypoxia could mediate its protective role via the activation of two transcription factors and, consecutively, changes in gene expression encoding different anti- and pro-apoptotic proteins. |
format | Text |
id | pubmed-3098009 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-30980092011-05-20 Anti-apoptotic role of HIF-1 and AP-1 in paclitaxel exposed breast cancer cells under hypoxia Flamant, Lionel Notte, Annick Ninane, Noelle Raes, Martine Michiels, Carine Mol Cancer Research BACKGROUND: Hypoxia is a hallmark of solid tumors and is associated with metastases, therapeutic resistance and poor patient survival. RESULTS: In this study, we showed that hypoxia protected MDA-MB-231 breast cancer cells against paclitaxel- but not epirubicin-induced apoptosis. The possible implication of HIF-1 and AP-1 in the hypoxia-induced anti-apoptotic pathway was investigated by the use of specific siRNA. Specific inhibition of the expression of these two transcription factors was shown to increase apoptosis induced by chemotherapeutic agents under hypoxia indicating an involvement of HIF-1 and AP-1 in the anti-apoptotic effect of hypoxia. After HIF-1 specific inhibition and using TaqMan Human Apoptosis Array, 8 potential HIF-1 target genes were identified which could take part in this protection. Furthermore, Mcl-1 was shown to be a potential AP-1 target gene which could also participate to the hypoxia-induced chemoresistance. CONCLUSIONS: Altogether, these data highlight two mechanisms by which hypoxia could mediate its protective role via the activation of two transcription factors and, consecutively, changes in gene expression encoding different anti- and pro-apoptotic proteins. BioMed Central 2010-07-13 /pmc/articles/PMC3098009/ /pubmed/20626868 http://dx.doi.org/10.1186/1476-4598-9-191 Text en Copyright ©2010 Flamant et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Flamant, Lionel Notte, Annick Ninane, Noelle Raes, Martine Michiels, Carine Anti-apoptotic role of HIF-1 and AP-1 in paclitaxel exposed breast cancer cells under hypoxia |
title | Anti-apoptotic role of HIF-1 and AP-1 in paclitaxel exposed breast cancer cells under hypoxia |
title_full | Anti-apoptotic role of HIF-1 and AP-1 in paclitaxel exposed breast cancer cells under hypoxia |
title_fullStr | Anti-apoptotic role of HIF-1 and AP-1 in paclitaxel exposed breast cancer cells under hypoxia |
title_full_unstemmed | Anti-apoptotic role of HIF-1 and AP-1 in paclitaxel exposed breast cancer cells under hypoxia |
title_short | Anti-apoptotic role of HIF-1 and AP-1 in paclitaxel exposed breast cancer cells under hypoxia |
title_sort | anti-apoptotic role of hif-1 and ap-1 in paclitaxel exposed breast cancer cells under hypoxia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098009/ https://www.ncbi.nlm.nih.gov/pubmed/20626868 http://dx.doi.org/10.1186/1476-4598-9-191 |
work_keys_str_mv | AT flamantlionel antiapoptoticroleofhif1andap1inpaclitaxelexposedbreastcancercellsunderhypoxia AT notteannick antiapoptoticroleofhif1andap1inpaclitaxelexposedbreastcancercellsunderhypoxia AT ninanenoelle antiapoptoticroleofhif1andap1inpaclitaxelexposedbreastcancercellsunderhypoxia AT raesmartine antiapoptoticroleofhif1andap1inpaclitaxelexposedbreastcancercellsunderhypoxia AT michielscarine antiapoptoticroleofhif1andap1inpaclitaxelexposedbreastcancercellsunderhypoxia |