IGFBP-3 hypermethylation-derived deficiency mediates cisplatin resistance in non-small-cell lung cancer
| Autor: | Rosario Machado-Pinilla, Manuel Nistal, Inmaculada Ibáñez de Cáceres, C. Moratilla, Rosario Perona, Cristobal Belda-Iniesta, Paloma Cejas, Luis Paz-Ares, Cristina Manguan-García, Fernando Lopez-Rios, María Cortes-Sempere, V. Rodriguez-Fanjul, J de Castro-Carpeño |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Lung Neoplasms Cell Survival Antineoplastic Agents Kaplan-Meier Estimate Biology Hydroxamic Acids Carcinoma Non-Small-Cell Lung Cell Line Tumor Tumor Cells Cultured Genetics medicine Humans Epigenetics Promoter Regions Genetic Lung cancer neoplasms Molecular Biology Oligonucleotide Array Sequence Analysis Regulation of gene expression Cisplatin Base Sequence Reverse Transcriptase Polymerase Chain Reaction Cancer Methylation DNA Methylation Cell cycle medicine.disease Molecular biology Gene Expression Regulation Neoplastic Insulin-Like Growth Factor Binding Protein 3 Drug Resistance Neoplasm DNA methylation Azacitidine Cancer research RNA Interference HT29 Cells HeLa Cells medicine.drug |
| Zdroj: | Oncogene. 29:1681-1690 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/onc.2009.454 |
| Popis: | Cisplatin-based chemotherapy is the paradigm of non-small-cell lung cancer (NSCLC) treatment; however, it also induces de novo DNA-hypermethylation, a process that may be involved in the development of drug-resistant phenotypes by inactivating genes required for drug-cytotoxicity. By using an expression microarray analysis, we aimed to identify those genes reactivated in a set of two cisplatin (CDDP) resistant and sensitive NSCLC cell lines after epigenetic treatment. Gene expression, promoter methylation and CDDP-chemoresponse were further analyzed in three matched sets of sensitive/resistant cell lines, 23 human cancer cell lines and 36 NSCLC specimens. Results revealed specific silencing by promoter hypermethylation of IGFBP-3 in CDDP resistant cells, whereas IGFBP-3 siRNA interference, induced resistance to CDDP in sensitive cells (P |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|