Hypoxia-induced modulation of apoptosis and BCL-2 family proteins in different cancer cell types
| Autor: | Carine Michiels, Amélie Maincent, Thierry Arnould, Maude Fransolet, Marie Genin, Audrey Sermeus, Annick Notte, Lionel Leclere, Hélène Riquier |
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| Rok vydání: | 2012 |
| Předmět: |
Programmed cell death
Cell type Paclitaxel Cell Cancer Treatment lcsh:Medicine Gene Expression Antineoplastic Agents Apoptosis Biology Models Biological Cell Line Tumor Neoplasms Molecular Cell Biology Basic Cancer Research medicine Genetics Cancer Genetics Humans Gene Silencing RNA Messenger lcsh:Science Etoposide Cellular Stress Responses A549 cell Multidisciplinary Gene Expression Profiling Bcl-2 family lcsh:R Hypoxia (medical) Chemotherapy and Drug Treatment Hypoxia-Inducible Factor 1 alpha Subunit Cell Hypoxia Cell biology Gene Expression Regulation Neoplastic medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 Oncology Cancer cell Medicine lcsh:Q medicine.symptom Tumor Suppressor Protein p53 DNA Damage Signal Transduction Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 11, p e47519 (2012) Sermeus, A, Genin, M, Maincent, A, Fransolet, M, Notte, A, Leclere, L, Riquier, H, Arnould, T & Michiels, C 2012, ' Hypoxia-induced modulation of apoptosis and BCL-2 family proteins in different cancer cell types ', PLoS ONE, vol. 7, no. 11, pp. e47519 . https://doi.org/10.1371/journal.pone.0047519 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0047519 |
| Popis: | Hypoxia plays an important role in the resistance of tumour cells to chemotherapy. However, the exact mechanisms underlying this process are not well understood. Moreover, according to the cell lines, hypoxia differently influences cell death. The study of the effects of hypoxia on the apoptosis induced by 5 chemotherapeutic drugs in 7 cancer cell types showed that hypoxia generally inhibited the drug-induced apoptosis. In most cases, the effect of hypoxia was the same for all the drugs in one cell type. The expression profile of 93 genes involved in apoptosis as well as the protein level of BCL-2 family proteins were then investigated. In HepG2 cells that are strongly protected against cell death by hypoxia, hypoxia decreased the abundance of nearly all the pro-apoptotic BCL-2 family proteins while none of them are decreased in A549 cells that are not protected against cell death by hypoxia. In HepG2 cells, hypoxia decreased NOXA and BAD abundance and modified the electrophoretic mobility of BIM(EL). BIM and NOXA are important mediators of etoposide-induced cell death in HepG2 cells and the hypoxia-induced modification of these proteins abundance or post-translational modifications partly account for chemoresistance. Finally, the modulation of the abundance and/or of the post-translational modifications of most proteins of the BCL-2 family by hypoxia involves p53-dependent and -independent pathways and is cell type-dependent. A better understanding of these cell-to-cell variations is crucial in order to overcome hypoxia-induced resistance and to ameliorate cancer therapy. |
| Databáze: | OpenAIRE |
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