Open AccessSTAT 1 facilitates oestrogen receptor α transcription and stimulates breast cancer cell proliferation
Author(s) -
Hou Yingxiang,
Li Xin,
Li Qianhua,
Xu Juntao,
Yang Huijie,
Xue Min,
Niu Gang,
Zhuo Shu,
Mu Kun,
Wu Gaosong,
Li Xiumin,
Wang Hui,
Zhu Jian,
Zhuang Ting
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13882
Subject(s) - cancer research , biology , tamoxifen , breast cancer , cell growth , signal transduction , stat , chromatin immunoprecipitation , cancer , microbiology and biotechnology , gene expression , promoter , gene , genetics , stat3
Oestrogen receptor α ( ER α) is overexpressed in two‐thirds of all breast cancer cases and is involved in breast cancer development and progression. Although ER α ‐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 ER α 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 ( LCC 2) 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 ISGF 3 complex. As the critical effectors, STAT 1 and IRF 9 were up‐regulated 5‐ and 20‐fold, respectively, in LCC 2 cells. The biological experiments indicated that STAT 1 is important for ER α signalling. Depletion of STAT 1 or inhibition of STAT 1 function significantly decreased levels of ER α protein, ER α ‐target gene expression and cell proliferation in both the MCF ‐7 and LCC 2 cell lines. Chromatin immunoprecipitation revealed that ER α transcription is associated with STAT 1 recruitment to the ER α promoter region, suggesting that transcriptional regulation is one mechanism by which STAT 1 regulates ER α mRNA levels and ER α signalling in breast cancer cells. The present study reveals a possible endocrine‐resistant mechanism by which STAT 1 modulates ER α signalling and confers tamoxifen resistance. Targeting of STAT 1 is a potential treatment strategy for endocrine‐resistant breast cancers.