Author:
Flamant Lionel,Notte Annick,Ninane Noelle,Raes Martine,Michiels Carine
Abstract
Abstract
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.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Molecular Medicine
Reference64 articles.
1. Vaupel P, Schlenger K, Knoop C, Hockel M: Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements. Cancer Res. 1991, 51: 3316-3322.
2. Chun YS, Adusumilli PS, Fong Y: Employing tumor hypoxia for oncolytic therapy in breast cancer. J Mammary Gland Biol Neoplasia. 2005, 10: 311-318. 10.1007/s10911-006-9004-6
3. Brown JM, Giaccia AJ: The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res. 1998, 58: 1408-1416.
4. Hockel M, Vaupel P: Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst. 2001, 93: 266-276. 10.1093/jnci/93.4.266
5. Teicher BA: Hypoxia and drug resistance. Cancer Metastasis Rev. 1994, 13: 139-168. 10.1007/BF00689633
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