[曲妥珠单抗耐药乳腺癌细胞系BT-474的转录组学分析]。

Q3 Medicine
S A Shifon, I O Karpets, A S Chesnokova, P E Karitskaya, E O Ukladov, I V Evgenov, S V Sidorov, L F Gulyaeva
{"title":"[曲妥珠单抗耐药乳腺癌细胞系BT-474的转录组学分析]。","authors":"S A Shifon, I O Karpets, A S Chesnokova, P E Karitskaya, E O Ukladov, I V Evgenov, S V Sidorov, L F Gulyaeva","doi":"10.31857/S0026898425040041","DOIUrl":null,"url":null,"abstract":"<p><p>The development of resistance to trastuzumab in HER2-positive breast cancer is a serious clinical problem that limits the effectiveness of targeted therapy. In a significant proportion of patients, the mechanisms in the development of resistance remain poorly understood. The BT-474 cell line was selected as an optimal model for study because it represents a HER2-positive luminal B subtype breast cancer cell line. To identify the molecular mechanisms of resistance, a comprehensive transcriptomic analysis based on RNA-seq data comparison of three independent datasets including both sensitive and trastuzumab-resistant variants was applied. The methodological approach included multistep bioinformatics analysis followed by identification of regulatory interactions. The study identified genes with increased expression (FUCA2, HSPE1, SHLD1, NMD3) and genes with decreased expression (GPC5, FSTL1, ATG16L2, POLD2) in resistant cells. Key transcription factors (E2F1, MYC, YBX1, HEY1, NFIC, TFAP2A, AP-1/JUN, NCOA1) regulating the expression of the detected genes during the development of resistance were identified. The changes identified indicate a complex reprogramming of transcriptional activity affecting cell cycle processes, DNA repair, metabolism, and the epithelial-mesenchymal transition. The findings expand our understanding of the molecular mechanisms of trastuzumab resistance and open prospects for the development of novel therapeutic strategies to overcome drug resistance in HER2-positive breast cancer.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"59 4","pages":"572-586"},"PeriodicalIF":0.0000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[Transcriptomic Profile of the Trastuzumab-Resistant Breast Cancer Cell Line BT-474].\",\"authors\":\"S A Shifon, I O Karpets, A S Chesnokova, P E Karitskaya, E O Ukladov, I V Evgenov, S V Sidorov, L F Gulyaeva\",\"doi\":\"10.31857/S0026898425040041\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The development of resistance to trastuzumab in HER2-positive breast cancer is a serious clinical problem that limits the effectiveness of targeted therapy. In a significant proportion of patients, the mechanisms in the development of resistance remain poorly understood. The BT-474 cell line was selected as an optimal model for study because it represents a HER2-positive luminal B subtype breast cancer cell line. To identify the molecular mechanisms of resistance, a comprehensive transcriptomic analysis based on RNA-seq data comparison of three independent datasets including both sensitive and trastuzumab-resistant variants was applied. The methodological approach included multistep bioinformatics analysis followed by identification of regulatory interactions. The study identified genes with increased expression (FUCA2, HSPE1, SHLD1, NMD3) and genes with decreased expression (GPC5, FSTL1, ATG16L2, POLD2) in resistant cells. Key transcription factors (E2F1, MYC, YBX1, HEY1, NFIC, TFAP2A, AP-1/JUN, NCOA1) regulating the expression of the detected genes during the development of resistance were identified. The changes identified indicate a complex reprogramming of transcriptional activity affecting cell cycle processes, DNA repair, metabolism, and the epithelial-mesenchymal transition. The findings expand our understanding of the molecular mechanisms of trastuzumab resistance and open prospects for the development of novel therapeutic strategies to overcome drug resistance in HER2-positive breast cancer.</p>\",\"PeriodicalId\":39818,\"journal\":{\"name\":\"Molekulyarnaya Biologiya\",\"volume\":\"59 4\",\"pages\":\"572-586\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molekulyarnaya Biologiya\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.31857/S0026898425040041\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molekulyarnaya Biologiya","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.31857/S0026898425040041","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0

摘要

her2阳性乳腺癌中曲妥珠单抗耐药的发展是一个严重的临床问题,限制了靶向治疗的有效性。在相当大比例的患者中,耐药性发展的机制仍然知之甚少。选择BT-474细胞系作为研究的最佳模型,因为它代表了her2阳性的管腔B亚型乳腺癌细胞系。为了确定耐药的分子机制,应用基于RNA-seq数据比较的三个独立数据集(包括敏感和曲妥珠单抗耐药变体)的综合转录组学分析。方法方法包括多步骤生物信息学分析,然后确定调控相互作用。研究发现耐药细胞中表达升高的基因(FUCA2、HSPE1、SHLD1、NMD3)和表达降低的基因(GPC5、FSTL1、ATG16L2、POLD2)。鉴定出在耐药过程中调控检测基因表达的关键转录因子(E2F1、MYC、YBX1、HEY1、NFIC、TFAP2A、AP-1/JUN、NCOA1)。所发现的变化表明,转录活性的复杂重编程影响细胞周期过程、DNA修复、代谢和上皮-间质转化。这些发现扩大了我们对曲妥珠单抗耐药的分子机制的理解,并为开发克服her2阳性乳腺癌耐药的新治疗策略开辟了前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Transcriptomic Profile of the Trastuzumab-Resistant Breast Cancer Cell Line BT-474].

The development of resistance to trastuzumab in HER2-positive breast cancer is a serious clinical problem that limits the effectiveness of targeted therapy. In a significant proportion of patients, the mechanisms in the development of resistance remain poorly understood. The BT-474 cell line was selected as an optimal model for study because it represents a HER2-positive luminal B subtype breast cancer cell line. To identify the molecular mechanisms of resistance, a comprehensive transcriptomic analysis based on RNA-seq data comparison of three independent datasets including both sensitive and trastuzumab-resistant variants was applied. The methodological approach included multistep bioinformatics analysis followed by identification of regulatory interactions. The study identified genes with increased expression (FUCA2, HSPE1, SHLD1, NMD3) and genes with decreased expression (GPC5, FSTL1, ATG16L2, POLD2) in resistant cells. Key transcription factors (E2F1, MYC, YBX1, HEY1, NFIC, TFAP2A, AP-1/JUN, NCOA1) regulating the expression of the detected genes during the development of resistance were identified. The changes identified indicate a complex reprogramming of transcriptional activity affecting cell cycle processes, DNA repair, metabolism, and the epithelial-mesenchymal transition. The findings expand our understanding of the molecular mechanisms of trastuzumab resistance and open prospects for the development of novel therapeutic strategies to overcome drug resistance in HER2-positive breast cancer.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Molekulyarnaya Biologiya
Molekulyarnaya Biologiya Medicine-Medicine (all)
CiteScore
0.70
自引率
0.00%
发文量
131
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信