Nuclear factor-ĸB plays a critical role in both intrinsic and acquired resistance against endocrine therapy in human breast cancer cells.
Nuclear factor-ĸB plays a critical role in both intrinsic and acquired resistance against endocrine therapy in human breast cancer cells.
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DOI：
10.1038/srep04057
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发表时间：
2014-02-17
影响因子：
4.6
通讯作者：
Tanaka A
中科院分区：
文献类型：
--
作者：
Oida K;Matsuda A;Jung K;Xia Y;Jang H;Amagai Y;Ahn G;Nishikawa S;Ishizaka S;Jensen-Jarolim E;Matsuda H;Tanaka A
由于75%以上的乳腺癌过表达雌激素受体（ER），针对ER的内分泌治疗显著提高了生存率。尽管如此，乳腺癌仍然困扰着全世界的女性，其背后的主要问题是对内分泌治疗的耐药性。我们之前已经证明核因子-κB （NF-κB）参与人乳腺癌细胞的肿瘤增殖；然而，与er阳性细胞转化的关系尚不清楚。在目前的研究中，我们主要通过er阳性MCF-7细胞研究NF-κB在乳腺癌激素依赖中的作用。阻断NF-κB信号通过下调d型细胞周期蛋白抑制er阴性细胞的增殖。相反，MCF-7细胞对NF-κB抑制有抵抗性。在无雌激素条件下，与原始MCF-7细胞相比，ER水平降低，建立的细胞亚群表现出他莫昔芬抗性。此外，NF-κB参与细胞生长，而不是亚线中的雌激素- er轴，从而干扰NF-κB信号，诱导他莫昔芬的附加抗癌作用。NF-κB抑制抑制了负责细胞迁移和细胞在体内扩增的MMP-9的产生。因此，我们认为NF-κB在er阳性和er阴性乳腺癌中都是一个主开关。
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.
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DOI：
10.1073/pnas.48.6.1014
发表时间：
1962-01-01
影响因子：
11.1
作者：
GROSS, J;LAPIERE, CM
通讯作者：
LAPIERE, CM
影响因子：
82.9
作者：
Pan, Xin;Zhou, Tao;Zhang, Xue-Min
通讯作者：
Zhang, Xue-Min
影响因子：
11.4
作者：
Barre, Benjamin;Perkins, Neil D.
通讯作者：
Perkins, Neil D.
影响因子：
45.3
作者：
Harvey, JM;Clark, GM;Allred, DC
通讯作者：
Allred, DC
影响因子：
45.3
作者：
Hammond, M. Elizabeth H.;Hayes, Daniel F.;Wolff, Antonio C.
通讯作者：
Wolff, Antonio C.