TMEM45A is essential for hypoxia-induced chemoresistance in breast and liver cancer cells
| Autor: | Christiane Sterpin, Carine Michiels, Lionel Flamant, Aurélie Hayez, Michael Pierre, Olivier De Backer, Thierry Arnould, Yves Poumay, Edith Roegiers |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Keratinocytes
CA15-3 Programmed cell death Cancer Research Paclitaxel Cell Survival Microarrays Blotting Western Antineoplastic Agents Breast Neoplasms Apoptosis Kaplan-Meier Estimate Biology lcsh:RC254-282 Transcriptome Cell Line Tumor medicine Genetics Humans Gene silencing Hypoxia Cells Cultured Etoposide Epirubicin Oligonucleotide Array Sequence Analysis Cancer Reverse Transcriptase Polymerase Chain Reaction Liver Neoplasms Membrane Proteins Hep G2 Cells lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell Hypoxia Gene Expression Regulation Neoplastic Oncology Drug Resistance Neoplasm Cancer cell Cancer research Female RNA Interference Gene expression Stem cell Chemoresistance Research Article medicine.drug |
| Zdroj: | BMC Cancer, Vol 12, Iss 1, p 391 (2012) BMC Cancer |
| ISSN: | 1476-4598 |
| DOI: | 10.1186/1471-2407-12-391 |
| Popis: | Background Hypoxia is a common characteristic of solid tumors associated with reduced response to radio- and chemotherapy, therefore increasing the probability of tumor recurrence. The aim of this study was to identify new mechanisms responsible for hypoxia-induced resistance in breast cancer cells. Methods MDA-MB-231 and HepG2 cells were incubated in the presence of taxol or etoposide respectively under normoxia and hypoxia and apoptosis was analysed. A whole transcriptome analysis was performed in order to identify genes whose expression profile was correlated with apoptosis. The effect of gene invalidation using siRNA was studied on drug-induced apoptosis. Results MDA-MB-231 cells incubated in the presence of taxol were protected from apoptosis and cell death by hypoxia. We demonstrated that TMEM45A expression was associated with taxol resistance. TMEM45A expression was increased both in MDA-MB-231 human breast cancer cells and in HepG2 human hepatoma cells in conditions where protection of cells against apoptosis induced by chemotherapeutic agents was observed, i.e. under hypoxia in the presence of taxol or etoposide. Moreover, this resistance was suppressed by siRNA-mediated silencing of TMEM45A. Kaplan Meier curve showed an association between high TMEM45A expression and poor prognostic in breast cancer patients. Finally, TMEM45 is highly expressed in normal differentiated keratinocytes both in vitro and in vivo, suggesting that this protein is involved in epithelial functions. Conclusion Altogether, our results unravel a new mechanism for taxol and etoposide resistance mediated by TMEM45A. High levels of TMEM45A expression in tumors may be indicative of potential resistance to cancer therapy, making TMEM45A an interesting biomarker for resistance. |
| Databáze: | OpenAIRE |
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