Open AccessRNF 168 facilitates oestrogen receptor ɑ transcription and drives breast cancer proliferation
Author(s) -
Liu Zhenhua,
Zhang Jinghang,
Xu Juntao,
Yang Huijie,
Li Xin,
Hou Yingxiang,
Zhao Yan,
Xue Min,
Wang Beibei,
Yu Na,
Yu Sifan,
Niu Gang,
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.13694
Subject(s) - breast cancer , chromatin immunoprecipitation , cancer research , cell growth , flow cytometry , cancer , biology , transcription factor , western blot , medicine , gene expression , microbiology and biotechnology , gene , promoter , genetics
Oestrogen receptor ɑ ( ER ɑ) is overexpressed in two‐thirds of all breast cancers and involves in development and breast cancer progression. Although ER ɑ‐positive breast cancer could be effective treated by endocrine therapy, the endocrine resistance is still an urgent clinical problem. Thus, further understanding of the underlying mechanisms ER ɑ signalling is critical in dealing with endocrine resistance in breast cancer patients. MCF ‐7 and T47D breast cancer cell lines are used to carry out the molecular biological experiments. Western blot is used to assess the relative protein level of ER ɑ, RNF 168 and actin. Real‐time PCR is used the measure the relative ER ɑ‐related gene mRNA level. Luciferase assay is used to measure the relative ER ɑ signalling activity. Chromatin immunoprecipitation is used to measure the RNF 168 binding affinity to ER ɑ promoter regions. WST assay and flow cytometry are used to measure the cell proliferation capacity. We use Student's t test and one‐way ANOVA test for statistical data analysis. Here, we report an important role in ER ɑ‐positive breast cancer cells for RNF 168 protein in supporting cell proliferation by driving the transcription of ER ɑ. RNF 168 is highly expressed in breast cancer samples, compared with normal breast tissue. In patients with breast cancer, RNF 168 expression level is correlated with poor endocrine treatment outcome. Depletion of RNF 168 causes decreased cell proliferation in MCF ‐7 and T47D cells. Besides, depletion RNF 168 reduced mRNA level of ER ɑ and its target genes, such as PS 2 and GREB 1. Chromatin immunoprecipitation revealed that ER ɑ transcription is associated with RNF 168 recruitment to ER ɑ promoter region, suggesting that transcriptional regulation is one mechanism by which RNF 168 regulates ER ɑ mRNA level and ER ɑ signalling in breast cancer cells. RNF 168 is required for ER ɑ‐positive breast cancer cell proliferation and facilitate ER ɑ signalling activity possibly through promoting transcription of ERɑ.