STAT1 facilitates oestrogen receptor α transcription and stimulates breast cancer cell proliferation.
STAT1 facilitates oestrogen receptor α transcription and stimulates breast cancer cell proliferation.
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STAT1促进雌激素受体α转录并刺激乳腺癌细胞增殖
DOI：
10.1111/jcmm.13882
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发表时间：
2018-12
影响因子：
5.3
通讯作者：
Zhuang T
中科院分区：
文献类型：
--
作者：
Hou Y;Li X;Li Q;Xu J;Yang H;Xue M;Niu G;Zhuo S;Mu K;Wu G;Li X;Wang H;Zhu J;Zhuang T
雌激素受体α（ERα）在三分之二的乳腺癌病例中过表达，并参与乳腺癌的发生和进展。虽然ERα阳性乳腺癌可以通过内分泌治疗得到有效治疗，但内分泌抵抗是一个迫切的临床问题。因此，进一步了解ERα信号转导的潜在机制对于处理乳腺癌患者的内分泌抵抗至关重要。在本研究中，在MCF-7和MCF-7他莫昔芬耐药（LCC 2）细胞系之间进行无偏RNA序列分析，以鉴定差异表达的基因。整个转录组学数据表明JAK-STAT通路显著上调，特别是ISGF 3复合物。作为关键效应子，STAT 1和IRF 9在LCC 2细胞中分别上调5倍和20倍。生物学实验表明STAT 1在ERα信号通路中起重要作用。在MCF-7和LCC 2细胞系中，STAT 1的消耗或STAT 1功能的抑制显著降低了ERα蛋白、ERα靶基因表达和细胞增殖的水平。染色质免疫沉淀显示ERα转录与STAT 1募集到ERα启动子区相关，表明转录调节是STAT 1调节乳腺癌细胞ERα mRNA水平和ERα信号传导的一种机制。本研究揭示了一种可能的内分泌耐药机制，STAT 1通过该机制调节ERα信号传导并赋予他莫昔芬耐药性。靶向STAT 1是内分泌抵抗性乳腺癌的潜在治疗策略。
Oestrogen receptor α (ERα) is overexpressed in two‐thirds of all breast cancer cases and is involved in breast cancer development and progression. Although ERα ‐positive breast cancer can be effectively treated by endocrine therapy, endocrine resistance is an urgent clinical problem. Thus, further understanding of the underlying mechanisms involved in ERα signalling is critical in dealing with endocrine resistance in patients with breast cancer. In the present study, unbiased RNA sequence analysis was conducted between the MCF‐7 and MCF‐7 tamoxifen‐resistant (LCC2) cell lines in order to identify differentially expressed genes. The whole transcriptomic data indicated that the JAK‐STAT pathway is markedly up‐regulated, particularly the ISGF3 complex. As the critical effectors, STAT1 and IRF9 were up‐regulated 5‐ and 20‐fold, respectively, in LCC2 cells. The biological experiments indicated that STAT1 is important for ERα signalling. Depletion of STAT1 or inhibition of STAT1 function significantly decreased levels of ERα protein, ERα ‐target gene expression and cell proliferation in both the MCF‐7 and LCC2 cell lines. Chromatin immunoprecipitation revealed that ERα transcription is associated with STAT1 recruitment to the ERα promoter region, suggesting that transcriptional regulation is one mechanism by which STAT1 regulates ERα mRNA levels and ERα signalling in breast cancer cells. The present study reveals a possible endocrine‐resistant mechanism by which STAT1 modulates ERα signalling and confers tamoxifen resistance. Targeting of STAT1 is a potential treatment strategy for endocrine‐resistant breast cancers.
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影响因子：
10.3
作者：
Shou, J;Massarweh, S;Schiff, R
通讯作者：
Schiff, R
影响因子：
3.7
作者：
Huang R;Faratian D;Sims AH;Wilson D;Thomas JS;Harrison DJ;Langdon SP
通讯作者：
Langdon SP
影响因子：
64.5
作者：
Shiau, AK;Barstad, D;Greene, GL
通讯作者：
Greene, GL
DOI：
10.1016/s0960-0760(01)00190-x
发表时间：
2002-02-01
影响因子：
4.1
作者：
Filardo, EJ
通讯作者：
Filardo, EJ
他莫昔芬在乳腺癌中的分子机制和模式。
影响因子：
1.9
作者：
Ali S;Rasool M;Chaoudhry H;N Pushparaj P;Jha P;Hafiz A;Mahfooz M;Abdus Sami G;Azhar Kamal M;Bashir S;Ali A;Sarwar Jamal M
通讯作者：
Sarwar Jamal M