三阴性乳腺癌细胞系 MDA-MB-231 和 MDA-MB-436 中的 BET 定向 PROTACs。

IF 3 3区 医学 Q2 ONCOLOGY Breast Cancer Research and Treatment Pub Date : 2024-11-01 Epub Date: 2024-06-19 DOI:10.1007/s10549-024-07403-w
Maryana Teufelsbauer, Sandra Stickler, Marie-Therese Eggerstorfer, Dennis Clyde Hammond, Gerhard Hamilton
{"title":"三阴性乳腺癌细胞系 MDA-MB-231 和 MDA-MB-436 中的 BET 定向 PROTACs。","authors":"Maryana Teufelsbauer, Sandra Stickler, Marie-Therese Eggerstorfer, Dennis Clyde Hammond, Gerhard Hamilton","doi":"10.1007/s10549-024-07403-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to find whether the proliferation and migration of triple negative breast cancer (TNBC) cell lines can be reduced by treatment with bromodomain and extra-terminal domain (BET) inhibitor JQ1 and BET protein targeting chimeras (PROTACs) ARV-771 and MZ1.</p><p><strong>Methods: </strong>Cytotoxicity tests, scratch migration assays and western blot proteome profiler arrays for protein expression of cancer-related proteins were used to evaluate the impact of a BET-inhibitor and two BET-directed PROTACs on cell viability, migration and on protein expression.</p><p><strong>Results: </strong>JQ1 and the PROTACs MZ1 and ARV-771 significantly inhibited the growth and migration of the KRAS G13D-mutated MDA-MB-231 cells. In this cell line, the PROTACs suppressed the residual expression of ERBB2/HER2, 3 and 4 that are essential for the proliferation of breast cancer cells and this cell line proved sensitive to HER2 inhibitors. In contrast, the effects of the PROTACs on the protein expression of MDA-MB-436 cells mostly affected cytokines and their cognate receptors.</p><p><strong>Conclusion: </strong>The degradation of BET-protein by PROTACs demonstrated significant anti-proliferative effects. The KRAS-mutated MDA-MB-231 cells belong to the low-HER2 expressing tumors that have a poorer prognosis compared to HER2-null patients. Since first oral PROTACs against tumor hormone receptors are in clinical trials, this mode of tumor therapy is expected to become an important therapeutic strategy in the future treatment of TNBC.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452555/pdf/","citationCount":"0","resultStr":"{\"title\":\"BET-directed PROTACs in triple negative breast cancer cell lines MDA-MB-231 and MDA-MB-436.\",\"authors\":\"Maryana Teufelsbauer, Sandra Stickler, Marie-Therese Eggerstorfer, Dennis Clyde Hammond, Gerhard Hamilton\",\"doi\":\"10.1007/s10549-024-07403-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>This study aims to find whether the proliferation and migration of triple negative breast cancer (TNBC) cell lines can be reduced by treatment with bromodomain and extra-terminal domain (BET) inhibitor JQ1 and BET protein targeting chimeras (PROTACs) ARV-771 and MZ1.</p><p><strong>Methods: </strong>Cytotoxicity tests, scratch migration assays and western blot proteome profiler arrays for protein expression of cancer-related proteins were used to evaluate the impact of a BET-inhibitor and two BET-directed PROTACs on cell viability, migration and on protein expression.</p><p><strong>Results: </strong>JQ1 and the PROTACs MZ1 and ARV-771 significantly inhibited the growth and migration of the KRAS G13D-mutated MDA-MB-231 cells. In this cell line, the PROTACs suppressed the residual expression of ERBB2/HER2, 3 and 4 that are essential for the proliferation of breast cancer cells and this cell line proved sensitive to HER2 inhibitors. In contrast, the effects of the PROTACs on the protein expression of MDA-MB-436 cells mostly affected cytokines and their cognate receptors.</p><p><strong>Conclusion: </strong>The degradation of BET-protein by PROTACs demonstrated significant anti-proliferative effects. The KRAS-mutated MDA-MB-231 cells belong to the low-HER2 expressing tumors that have a poorer prognosis compared to HER2-null patients. Since first oral PROTACs against tumor hormone receptors are in clinical trials, this mode of tumor therapy is expected to become an important therapeutic strategy in the future treatment of TNBC.</p>\",\"PeriodicalId\":9133,\"journal\":{\"name\":\"Breast Cancer Research and Treatment\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452555/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Breast Cancer Research and Treatment\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10549-024-07403-w\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Breast Cancer Research and Treatment","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10549-024-07403-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/19 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

目的:本研究旨在探讨溴基底域和末端外域(BET)抑制剂JQ1和BET蛋白靶向嵌合体(PROTACs)ARV-771和MZ1是否能减少三阴性乳腺癌(TNBC)细胞系的增殖和迁移:方法:采用细胞毒性试验、划痕迁移试验和Western印迹蛋白质组图谱阵列检测癌症相关蛋白质的表达,评估一种BET抑制剂和两种BET靶向PROTACs对细胞活力、迁移和蛋白质表达的影响:结果:JQ1以及PROTACs MZ1和ARV-771显著抑制了KRAS G13D突变的MDA-MB-231细胞的生长和迁移。在该细胞系中,PROTACs抑制了乳腺癌细胞增殖所必需的ERBB2/HER2、3和4的残余表达,证明该细胞系对HER2抑制剂敏感。相比之下,PROTACs 对 MDA-MB-436 细胞蛋白表达的影响主要涉及细胞因子及其同源受体:结论:PROTACs 对 BET 蛋白的降解具有显著的抗增殖作用。KRAS突变的MDA-MB-231细胞属于低HER2表达肿瘤,与HER2缺失患者相比预后较差。由于首个针对肿瘤激素受体的口服 PROTACs 已进入临床试验阶段,这种肿瘤治疗模式有望成为未来治疗 TNBC 的重要治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
BET-directed PROTACs in triple negative breast cancer cell lines MDA-MB-231 and MDA-MB-436.

Purpose: This study aims to find whether the proliferation and migration of triple negative breast cancer (TNBC) cell lines can be reduced by treatment with bromodomain and extra-terminal domain (BET) inhibitor JQ1 and BET protein targeting chimeras (PROTACs) ARV-771 and MZ1.

Methods: Cytotoxicity tests, scratch migration assays and western blot proteome profiler arrays for protein expression of cancer-related proteins were used to evaluate the impact of a BET-inhibitor and two BET-directed PROTACs on cell viability, migration and on protein expression.

Results: JQ1 and the PROTACs MZ1 and ARV-771 significantly inhibited the growth and migration of the KRAS G13D-mutated MDA-MB-231 cells. In this cell line, the PROTACs suppressed the residual expression of ERBB2/HER2, 3 and 4 that are essential for the proliferation of breast cancer cells and this cell line proved sensitive to HER2 inhibitors. In contrast, the effects of the PROTACs on the protein expression of MDA-MB-436 cells mostly affected cytokines and their cognate receptors.

Conclusion: The degradation of BET-protein by PROTACs demonstrated significant anti-proliferative effects. The KRAS-mutated MDA-MB-231 cells belong to the low-HER2 expressing tumors that have a poorer prognosis compared to HER2-null patients. Since first oral PROTACs against tumor hormone receptors are in clinical trials, this mode of tumor therapy is expected to become an important therapeutic strategy in the future treatment of TNBC.

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
CiteScore
6.80
自引率
2.60%
发文量
342
审稿时长
1 months
期刊介绍: Breast Cancer Research and Treatment provides the surgeon, radiotherapist, medical oncologist, endocrinologist, epidemiologist, immunologist or cell biologist investigating problems in breast cancer a single forum for communication. The journal creates a "market place" for breast cancer topics which cuts across all the usual lines of disciplines, providing a site for presenting pertinent investigations, and for discussing critical questions relevant to the entire field. It seeks to develop a new focus and new perspectives for all those concerned with breast cancer.
期刊最新文献
Correction: FBLN2 is associated with basal cell markers Krt14 and ITGB1 in mouse mammary epithelial cells and has a preferential expression in molecular subtypes of human breast cancer. A randomised trial comparing 6-monthly adjuvant zoledronate with a single one-time dose in patients with early breast cancer. Alterations in the expression of homologous recombination repair (HRR) genes in breast cancer tissues considering germline BRCA1/2 mutation status. Efficacy of antiobesity medications among breast cancer survivors taking aromatase inhibitors. Cost containment analysis of superparamagnetic iron oxide (SPIO) injection in patients with ductal carcinoma in situ.
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1