首页> 美国卫生研究院文献>Scientific Reports >Nuclear factor-ĸB plays a critical role in both intrinsic and acquired resistance against endocrine therapy in human breast cancer cells
【2h】

Nuclear factor-ĸB plays a critical role in both intrinsic and acquired resistance against endocrine therapy in human breast cancer cells

机译:核因子-ĸB在人类乳腺癌细胞内分泌治疗和获得性耐药中均起着关键作用

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。
获取外文期刊封面目录资料

摘要

Since more than 75% of breast cancers overexpress estrogen receptors (ER), endocrine therapy targeting ER has significantly improved the survival rate. Nonetheless, breast cancer still afflicts women worldwide and the major problem behind it is resistance to endocrine therapy. We have previously shown the involvement of nuclear factor-κB (NF-κB) in neoplastic proliferation of human breast cancer cells; however, the association with the transformation of ER-positive cells remains unclear. In the current study, we focused on roles of NF-κB in the hormone dependency of breast cancers by means of ER-positive MCF-7 cells. Blocking of NF-κB signals in ER-negative cells stopped proliferation by downregulation of D-type cyclins. In contrast, the MCF-7 cells were resistant to NF-κB inhibition. Under estrogen-free conditions, the ER levels were reduced when compared with the original MCF-7 cells and the established cell subline exhibited tamoxifen resistance. Additionally, NF-κB participated in cell growth instead of the estrogen-ER axis in the subline and consequently, interfering with the NF-κB signals induced additive anticancer effects with tamoxifen. MMP-9 production responsible for cell migration, as well as the cell expansion in vivo, were suppressed by NF-κB inhibition. Therefore, we suggest that NF-κB is a master switch in both ER-positive and ER-negative breast cancers.
机译:由于超过75%的乳腺癌过表达雌激素受体(ER),针对ER的内分泌治疗显着提高了生存率。尽管如此,乳腺癌仍然困扰着全世界的妇女,其背后的主要问题是对内分泌治疗的抵抗力。先前我们已经表明核因子-κB(NF-κB)参与了人类乳腺癌细胞的肿瘤增殖。然而,与ER阳性细胞转化的关联仍不清楚。在当前的研究中,我们集中于NF-κB通过ER阳性MCF-7细胞在乳腺癌激素依赖中的作用。 ER阴性细胞中NF-κB信号的阻断通过D型细胞周期蛋白的下调停止了增殖。相反,MCF-7细胞对NF-κB抑制有抗性。在无雌激素的条件下,与原始MCF-7细胞相比,ER水平降低,并且建立的细胞亚系显示出他莫昔芬耐药性。此外,NF-κB参与了亚系中的细胞生长而不是雌激素-ER轴,因此,干扰NF-κB信号诱导了他莫昔芬的加性抗癌作用。负责细胞迁移以及体内细胞扩增的MMP-9产生被NF-κB抑制所抑制。因此,我们建议NF-κB是ER阳性和ER阴性乳腺癌中的主要开关。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号