Two different docetaxel resistant MCF-7 sublines exhibited different gene expression pattern

被引:22
作者
Iseri, Ozlem Darcansoy [1 ]
Kars, Meltem Demirel [1 ]
Gunduz, Ufuk [1 ]
机构
[1] Middle E Tech Univ, Dept Biol Sci, TR-06531 Ankara, Turkey
关键词
Multidrug resistance; MCF-7; Docetaxel; cDNA microarray; TISSUE GROWTH-FACTOR; MICROTUBULE-ASSOCIATED PROTEIN-1B; BREAST-CANCER CELLS; DRUG-RESISTANCE; P-GLYCOPROTEIN; UP-REGULATION; IN-VITRO; BCL-2-BINDING PROTEIN; HUMAN CYP1B1; APOPTOSIS;
D O I
10.1007/s11033-011-1123-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The objective of the present study was to investigate gene expression pattern of two docetaxel resistant MCF-7 breast carcinoma sublines step wisely selected in 30 and 120 nM docetaxel. Cell proliferation assay was performed in order to demonstrate development of docetaxel resistance. cDNA microarray analysis was performed using Affymetrix(A (R)) Human Genome U133 Plus 2.0 Arrays in duplicate experiments. Quantitative and semi-quantitative gene expression analysis was also performed to confirm gene expression analysis for selected genes. XTT results demonstrated that 30 (MCF-7/30nM DOC) and 120 nM (MCF-7/120nM DOC) docetaxel selected cells were 13- and 47-fold resistant, respectively. cDNA microarray analysis demonstrated that expression profiles of MCF-7 and MCF-7/30nM DOC were more similar to each other where expression profile of MCF-7/120nM DOC was different as examined by line graphs and scatter plots. 2,837 and 4,036 genes were significantly altered in 30 and 120 nM docetaxel resistant sublines, respectively. Among these, 849 genes were altered in common in two docetaxel resistant sublines. Antiapoptotic gene expression (e.g., Bcl-2 and APRIL) were noticeably altered in MCF-7/30nM DOC. However, docetaxel resistance in MCF-7/120nM DOC were more complicated with the involvement of ECM related gene expression, cytokine and growth factor signaling, ROS metabolism and EMT related gene expression together with higher level of MDR1 expression. Expression profiles in 30 and 120 nM docetaxel resistant sublines changed gradually with increasing resistance index. Drug resistance development seems to be step wise event in MCF-7 cells.
引用
收藏
页码:3505 / 3516
页数:12
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