Show/Hide Menu
Hide/Show Apps
Logout
Türkçe
Türkçe
Search
Search
Login
Login
OpenMETU
OpenMETU
About
About
Open Science Policy
Open Science Policy
Communities & Collections
Communities & Collections
Help
Help
Frequently Asked Questions
Frequently Asked Questions
Guides
Guides
Thesis submission
Thesis submission
MS without thesis term project submission
MS without thesis term project submission
Publication submission with DOI
Publication submission with DOI
Publication submission
Publication submission
Supporting Information
Supporting Information
General Information
General Information
Copyright, Embargo and License
Copyright, Embargo and License
Contact us
Contact us
Differential gene expression analysis in drug resistant multiple myeloma cell lines
Download
index.pdf
Date
2009
Author
Mutlu, Pelin
Metadata
Show full item record
Item Usage Stats
107
views
66
downloads
Cite This
The emergence of drug-resistance of tumor cells is a major complication for succesful chemotherapy. In this study, the molecular mechanisms of resistance to prednisone, vincristine and melphalan in multiple myeloma cell lines, RPMI-8226 and U-266 were investigated. Drug resistance was induced by application of the drugs by stepwise dose increments and confirmed by XTT cytotoxicity assay. Gene expression analysis demostrated that MDR1 gene is one of the most important factor causing the multidrug resistance phenotype in prednisone, vincristine and melphalan resistant multiple myeloma cell lines. According to microarray analysis alterations in laminin, integrin and collagen genes were detected. Additionally, upregulation of some oncogenes and growth factors (Rho family of GTPases, YES1, ACT2, TGFBR, EPS15, PDGF) was shown to have a role in MDR in multiple myeloma. Significant downregulation of suppressors of cytokine signalling gene expressions and upregulation of different types of interleukine and interferon gene expressions (IL3 and interferon-gamma receptor) which are related to JAK-STAT signalling pathay was shown. Alterations in expression levels of genes related to ceramide metabolism were shown especially for melphalan resistance in multiple myeloma. The data from vincristine/prednisone and vincristine/melphalan drug combination studies were shown that the usage of vincristine on prednisone and melphalan resistant multiple myeloma cell lines increase the efficacy of the chemotherapy. On the other hand the cross-resistance development of prednisone and melphalan resistant sublines to irradiation was detected. These results may help to understand the molecular mechanisms of prednisone, vincristine and melphalan resistance in multiple myeloma model cell lines RPMI-8226 and U-266.
Subject Keywords
Biology.
,
Genetics.
URI
http://etd.lib.metu.edu.tr/upload/3/12610970/index.pdf
https://hdl.handle.net/11511/18974
Collections
Graduate School of Natural and Applied Sciences, Thesis
Suggestions
OpenMETU
Core
Functional characterization of two potential breast cancer related genes
Akhavantabasi, Shiva; Erson Bensan, Ayşe Elif; Department of Biology (2012)
Cancer may arise as a result of deregulation of oncogenes and/or tumor suppressors. Although much progress has been made for the identification of such cancer related genes, our understanding of the complex tumorigenesis pathways is still not complete. Therefore, to improve our understanding of how certain basic mechanisms work in normal and in cancer cells, we aimed to characterize two different breast cancer related genes. First part of the study focused on subcellular localization USP32 (Ubiquitin Specif...
Investigation of docetaxel and doxorubicin resistance in mcf-7 breast carcinoma cell line
Darcansoy İşeri, Özlem; Gündüz, Ufuk; Department of Biotechnology (2009)
Multidrug resistance phenotype of tumor cells describes resistance to wide range of structurally unrelated anticancer agents and is a serious limitation to effective chemotherapy. It is a multifactor yet not fully elucidated phenomenon by the involvement of diverse cellular pathways. Aim of this study was to investigate the resistance mechanisms developed against docetaxel and doxorubicin that are widely used in the treatment of breast cancer in model cell line MCF-7. Resistant sublines were developed by ap...
Epigenetic Mechanisms Underlying the Dynamic Expression of Cancer-Testis Genes, PAGE2, -2B and SPANX-B, during Mesenchymal-to-Epithelial Transition
Yilmaz-Ozcan, Sinem; Sade, Asli; Kucukkaraduman, Baris; Kaygusuz, Yasemin; Senses, Kerem Mert; Banerjee, Sreeparna; GÜRE, ALİ OSMAY (Public Library of Science (PLoS), 2014-09-17)
Cancer-testis (CT) genes are expressed in various cancers but not in normal tissues other than in cells of the germline. Although DNA demethylation of promoter-proximal CpGs of CT genes is linked to their expression in cancer, the mechanisms leading to demethylation are unknown. To elucidate such mechanisms we chose to study the Caco-2 colorectal cancer cell line during the course of its spontaneous differentiation in vitro, as we found CT genes, in particular PAGE2, -2B and SPANX-B, to be up-regulated duri...
Differential alteration of IL-8 in liver cancer stem cell enrichment in response to PI3K/Akt/mTOR inhibitors and sorafenib
Kahraman, Deniz Cansen; Kahraman, Tamer; Atalay, Rengül (2018-07-01)
Liver cancer stem cells (LCSCs) are derived from damaged and transformed hepatic progenitor cells (HPCs) during precancerous cirrhosis stage. Ras/Raf/MAPK and PI3K/AKT/mTOR signaling pathways are significantly deregulated in liver cancer. The activation of PI3K/AKT/mTOR pathway in LCSC population is one of the reasons for acquired resistance to sorafenib in advanced hepatocellular carcinoma (HCC) patients. Therefore, identifying novel inhibitors targeting this pathway acting on LCSCs is highly essential. We...
Preparation of polyethylene glycol coated magnetic nanoparticles for targeting of cancer cells
Keskin, Tuğba; Gündüz, Ufuk; Department of Biology (2012)
Conventional cancer chemotherapies cannot differentiate between healthy and cancer cells, and lead to severe side effects and systemic toxicity. In the last decades, different kinds of controlled drug delivery systems have been developed to overcome these shortcomings of chemotherapeutics. Magnetic nanoparticles (MNP) are potentially important in cancer treatment since they can be targeted to tumor site by an externally applied magnetic field. In this study, it is aimed to synthesize folic acid conjugated; ...
Citation Formats
IEEE
ACM
APA
CHICAGO
MLA
BibTeX
P. Mutlu, “Differential gene expression analysis in drug resistant multiple myeloma cell lines,” Ph.D. - Doctoral Program, Middle East Technical University, 2009.
