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

Date

2010-06-01

Author

Iseri, Ozlem D.
Kars, Meltem D.
Gündüz, Ufuk

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

140
views

0
downloads

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.

Subject Keywords

TUBB, Beta-tubulin isotypes, Multidrug resistance, Antimicrotubule drugs

URI

https://hdl.handle.net/11511/54102

Journal

UHOD-ULUSLARARASI HEMATOLOJI-ONKOLOJI DERGISI

Collections

Graduate School of Natural and Applied Sciences, Article

Suggestions

OpenMETU
Core

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....
Targeted co-delivery of doxorubicin and TPGS to breast cancer cells by PLGA coated magnetic nanoparticles Metin, Esra; Gündüz, Ufuk; Mutlu, Pelin; Department of Biotechnology (2017) Although conventional chemotherapy is the most common method for cancer treatment, it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given to body systemically, normal cells also effect as cancer cells. However, in recent years, targeted drug delivery has been developed to overcome these drawbacks.The targeting strategy can be changed depending on carrier types, but magnetic nanoparticles are commonly preferred due to their easy targetable features by using ext...
Drug selection for malignant melanoma using biomarkers generated by weighted gene co-expression network analysis (WGCNA) Alpsoy, Semih; Acar, Aybar Can; Güre, Ali Osmay; Department of Bioinformatics (2017) Chemotherapy is one of the widely applied treatment choices for cancer patients; however, it might not be effective in the majority of patients due to the inability of foreseeing which patients respond to which chemotherapeutic agents. In order to ascertain appropriate chemotherapy for patients, thus, drug biomarkers predicting the response of the patients to chemotherapy should be discovered and translated into clinical practice to decide the ideal chemotherapeutic agents in a patient-centric manner. In th...
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 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...

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.