Drug resistant breast cancer cells overexpress ETS1 gene.
OBJECTIVE
Multidrug resistance (MDR) is resistance to wide range of structurally unrelated anticancer agents. MDR is a serious limitation to the effective chemotherapy. Involvement of ETS1 overexpression in upregulation of MDR1 gene expression is implicated. In the present study the aim was to assess the involvement of ETS1 and the genes, which encode the proteins interacting with ETS1 in drug resistant MCF-7 breast cancer cells.


METHODS
Drug resistant sublines to paclitaxel (MCF-7/Pac), docetaxel (MCF-7Doc), vincristine (MCF-7/Vinc) and doxorubicin (MCF-7/Dox) 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. Microarray data was supported by immunocytochemistry and western blot for drug resistance protein, P-gp, encoded by MDR1 gene.


RESULTS
According to microarray data MDR1 and ETS1 genes were highly overexpressed in all of the resistant sublines. Matrix metalloproteinase-1 gene (MMP-1) was also tremendously upregulated only in vincristine resistant cells. Immunocytochemistry and western blot results confirmed that P-gp was highly overexpressed in resistant sublines compared to original MCF-7 cells.


CONCLUSIONS
High ETS1 expression levels in all resistant MCF-7 sublines may lead to the upregulation of the transcription of MDR1 gene. Overexpression of ETS1 gene in resistant cells may have contributed to the development of resistance in the cells. Furthermore, the significant upregulation of MMP1 and MMP9 in MCF-7/Vinc may also be related to an acquired invasive behavior of MCF-7 cell line due to vincristine treatment.
Kars
Meltem Demirel
MD
Department of Biological Sciences, Middle East Technical University, Eskisehir Yolu, 06531 Ankara, Turkey.
Işeri
Ozlem Darcansoy
OD
Gündüz
Ufuk
U
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D009857:Oncogenes; D017239:Paclitaxel / Q000494:pharmacology; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics* / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D043823:Taxoids; D000077143:Docetaxel; D014750:Vincristine; D004317:Doxorubicin; D020781:Matrix Metalloproteinase 1; D017239:Paclitaxel