A microarray based expression profiling of paclitaxel and vincristine resistant MCF-7 cells


DEMİREL KARS M., Iseri O. D. , GÜNDÜZ U.

EUROPEAN JOURNAL OF PHARMACOLOGY, vol.657, pp.4-9, 2011 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 657
  • Publication Date: 2011
  • Doi Number: 10.1016/j.ejphar.2011.02.001
  • Journal Name: EUROPEAN JOURNAL OF PHARMACOLOGY
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.4-9
  • Keywords: MCF-7, Multiple drug resistance, Microarray analysis, Paclitaxel, Vincristine, MICROTUBULE-ASSOCIATED PROTEIN, CHRONIC LYMPHOCYTIC-LEUKEMIA, HUMAN BREAST-CANCER, TUMOR MICROENVIRONMENT, TRANSCRIPTION FACTORS, MULTIDRUG-RESISTANCE, DRUG-RESISTANCE, GENE-EXPRESSION, APOPTOSIS, BRCA1

Abstract

Resistance to the broad spectrum of chemotherapeutic agents in cancer cell lines and tumors has been called multiple drug resistance (MDR). In this study, the molecular mechanisms of resistance to two anticancer agents (paclitaxel and vincristine) in mammary carcinoma cell line MCF-7 were investigated. Drug resistant sublines to paclitaxel (MCF-7/Pac) and vincristine (MCF-7/Vinc) that were developed from sensitive MCF-7 cells (MCF-7/S) were used. cDNA microarray analysis was performed for the RNA samples of sensitive and resistant cells in duplicate experiments. GeneSpring GX 7.3.1 Software was used in data analysis. The results indicated that the upregulation of MDR] gene is the dominating mechanism of the paclitaxel and vincristine drug resistance. Additionally the upregulation of the genes encoding the detoxifying enzymes (i.e. GSTP1) was observed. Significant downregulation of apoptotic genes (i.e. PDCD2/4/6/8) and upregulation of some cell cycle regulatory genes (CDKN2A, CCNA2 etc.) was seen which may be in close relation to MDR in breast cancer. Drug resistant cancer cells exhibit different gene expression patterns depending on drug treatment, and each drug resistance phenotype is probably genetically different. Further functional studies are needed to demonstrate the complete set of genes contributing to the drug resistance phenotype in breast cancer cells. (C) 2011 Elsevier B.V. All rights reserved.