Anti-apoptotic role of HIF-1 and AP-1 in paclitaxel exposed breast cancer cells under hypoxia

Molecular Cancer

Research

Carine Michiels¹  Lionel Flamant¹  Martine Raes¹  Annick Notte¹  Noelle Ninane¹ 

[1] Laboratory of Biochemistry and cellular Biology (URBC), NARILIS - NAmur Research Institute for LIfe Sciences, FUNDP-University of Namur, 61 rue de Bruxelles, 5000, Namur, Belgium;

关键词: Paclitaxel;    Hypoxic Condition;    Epirubicin;    Fenretinide;    Myeloid Cell Leukaemia Sequence;   

DOI  :  10.1186/1476-4598-9-191

 received in 2009-08-31, accepted in 2010-07-13,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundHypoxia is a hallmark of solid tumors and is associated with metastases, therapeutic resistance and poor patient survival.ResultsIn 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.ConclusionsAltogether, 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.

【 授权许可】

Unknown   
© Flamant et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. 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.