Drug Resistant MCF-7 Cells have Altered Expression Levels of beta-Tubulin Isotypes and Mutations in TUBB Gene

2010-06-01
Iseri, Ozlem D.
Kars, Meltem D.
Gündüz, Ufuk
Antimicrotubule agents paclitaxel, docetaxel and vincristine are used in treatment of breast cancer. They bind to beta-tubulin subunit of microtubules. Multidrug resistance developed against these drugs remains a serious clinical problem. Different beta-tubulin izotypes possess differential assembly/disassembly dynamics. In this study, expressions of beta-tubulin isotypes, and mutations in TUBE gene were investigated in paclitaxel, docetaxel and vincristine resistant MCF-7 breast carcinoma cell lines. Resistant sublines were developed in the laboratory by continuous drug applications in dose increments and development of resistance were assayed by cytotoxicity analysis. Gene expression levels of beta-tubulin isotypes were investigated by RT-PCR. Exon 4 of the TUBB gene was amplified by PCR and the products were sequenced for determination of mutations. According to expression analysis, mRNA levels of beta II-, beta III- and beta V-tubulin isotypes were significantly upregulated in paclitaxel and docetaxel resistant cells where they were significantly downregulated in vincristine resistant cells. Sequence analysis of exon 4 of TUBB gene coding for beta I-tubulin revealed that MCF-7/120nMDoc cells carry Gln-327 -> His mutation and MCF-7/120nMVinc cells have His-179 -> Pro mutation. In conclusion, differential expression levels of beta II-, beta III- and beta V-tubulin isotypes and mutations in TUBB gene were determined in paclitaxel, docetaxel and vincristine resistant MCF-7 cells. It was shown for the first time that beta V-tubulin expression level may be correlated to resistance to antimicrotubule drugs. Though more functional analysis is required, the data presented here provides an insight into mechanisms of paclitaxel, docetaxel and vincristine resistance through alterations in tubulin/microtubule system.
UHOD-ULUSLARARASI HEMATOLOJI-ONKOLOJI DERGISI

Suggestions

Multidrug Resistance Mediated by MRP1 Gene Overexpression in Breast Cancer Patients
Abaan, Ogan Demir; Mutlu, Pelin; Baran, Yusuf; Atalay, Can; Gündüz, Ufuk (2009-01-01)
Multidrug resistance (MDR) is a serious handicap towards the effective treatment of breast cancer patients. One of the most prevalent MDR mechanisms is through the overexpression of genes coding the proteins called Multidrug Resistance-associated Proteins (MRPs). The aim of this study was to investigate the expression of MRP1 in tumor tissues from breast cancer patients. In this study, a semi-quantitative RT-PCR approach was utilized. Our results suggest that MRP1 overexpression can mediate MDR in patients....
Reversal of breast cancer resistance protein mediated multidrug resistance in MCF7 breast adenocarcinoma cell line
Urfalı, Çağrı; Gündüz, Ufuk; Department of Biology (2011)
Resistance to various chemotherapeutic agents is a major problem in success of cancer chemotherapy. One of the primary reasons of development of multidrug resistance (MDR) is the overexpression of ATP binding cassette (ABC) transporter proteins. Breast cancer resistance protein (BCRP) belongs to ABC transporter family and encoded by ABCG2 gene. BCRP is mainly expressed in MDR1 (P-glycoprotein) lacking breast cancer cells. Overexpression of BCRP leads to efflux of chemotherapeutic agents at higher rates, the...
Targeting glucosylceramide synthase sensitizes imatinib-resistant chronic myeloid leukemia cells via endogenous ceramide accumulation
BARAN, YUSUF; Bielawski, Jacek; Gündüz, Ufuk; Ogretmen, Besim (2011-10-01)
Purpose Drug resistance presents a major obstacle for the treatment of some patients with chronic myeloid leukemia (CML). Pro-apoptotic ceramide mediates imatinib-induced apoptosis, and metabolism of ceramide by glucosylceramide synthase (GCS) activity, converting ceramide to glucosyl ceramide, might contribute to imatinib resistance. In this study, we investigated the role of ceramide metabolism by GCS in the regulation of imatinib-induced apoptosis in drug-sensitive and drug-resistant K562 and K562/IMA-0....
Targeting HIF1-alpha/miR-326/ITGA5 axis potentiates chemotherapy response in triple-negative breast cancer
Assidicky, Ridho; Tokat, Unal Metin; Tarman, Ibrahim Oguzhan; Saatci, Ozge; Ersan, Pelin Gulizar; Raza, Umar; Ogul, Hasan; Riazalhosseini, Yasser; Can, Tolga; Sahin, Ozgur (2022-03-01)
Purpose Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer that is frequently treated with chemotherapy. However, many patients exhibit either de novo chemoresistance or ultimately develop resistance to chemotherapy, leading to significantly high mortality rates. Therefore, increasing the efficacy of chemotherapy has potential to improve patient outcomes. Methods Here, we performed whole transcriptome sequencing (both RNA and small RNA-sequencing), coupled with network simu...
Upregulation of multi drug resistance genes in doxorubicin resistant human acute myelogeneous leukemia cells and reversal of the resistance
BARAN, YUSUF; Guer, Bala; Kaya, Pelin; Ural, Ali Ugur; Avcu, Ferit; Gündüz, Ufuk (2007-12-01)
The major problem in the treatment of acute myeloid leukemia (AML) patients results from multidrug resistance to administered anticancer agents. Drug resistance proteins, MDR1 and MRP1, which work as drug efflux pumps, can mediate the multidrug resistance of human leukemia cells. In this study, the mechanisms of resistance to doxorubicin-induced cell death in human HL60 AML cells were examined.
Citation Formats
O. D. Iseri, M. D. Kars, and U. Gündüz, “Drug Resistant MCF-7 Cells have Altered Expression Levels of beta-Tubulin Isotypes and Mutations in TUBB Gene,” UHOD-ULUSLARARASI HEMATOLOJI-ONKOLOJI DERGISI, pp. 75–83, 2010, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/54102.