The effect of DNA methyltransferase 3A suppression in progression of the resistance phenotype in breast cancer cells

Author:

Andreeva O. E.1ORCID,Sorokin D. V.2ORCID,Vinokurova S. V.1ORCID,Shchegolev Yu. Yu.1ORCID,Elkina N. V.1ORCID,Katargin A. N.1ORCID,Faskhutdinov R. S.1ORCID,Salnikova D. I.3ORCID,Scherbakov A. M.2ORCID,Krasil’nikov M. A.2ORCID

Affiliation:

1. N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

2. N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia; National Research Lobachevsky State University of Nizhny Novgorod

3. N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia; Gause Institute of New Antibiotics

Abstract

Introduction. Rearrangement of molecular pathways and activation of bypass signaling determine the progression of tumor cell resistance to various drugs. Study of the common features of resistant formation mechanisms is essential for breast and other cancer beneficial treatments.Materials and methods. The present work was performed on estrogen receptor α ERα-positive (ERα – estrogen receptor α) McF-7 breast cancer cells, established sublines resistant to the mTOR inhibitor rapamycin or antiestrogen tamoxifen, and ERα-negative MDA-MB-231 breast cancer cells. Methods used include MTT test, transient transfection, immunoblotting, real-time polymerase chain reaction and methylation analysis by bisulfite pyrosequencing.Results. We have shown that the resistance of breast cancer cells to targeted and hormonal drugs is associated with the suppression of DNA methyltransferase 3A (DNMT3A) and respective changes in DNA methylation; DNMT3A knockdown results in the partial resistance to both drugs demonstrating the pivotal role of DNMT3A suppression in the progression of cell resistance.Conclusion. Totally, the results obtained highlight the possible mechanism of tumor cell resistance to targeting/hormonal drugs based on the deregulation of DNMTs expression and demonstrate  direct connection between DNMT3A suppression and resistance progression.

Publisher

Publishing House ABV Press

Subject

Cancer Research,Biochemistry (medical),Genetics (clinical),Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3