title: MDC1 Enhances Estrogen Receptor-mediated Transactivation and Contributes to Breast Cancer Suppression.
abstract: Estrogen receptor α (ERα) is a key transcriptional factor in the proliferation and differentiation in mammary epithelia and has been determined to be an important predictor of breast cancer prognosis and therapeutic target. Meanwhile, diverse transcriptional co-regulators of ERα play crucial and complicated roles in breast cancer progression. Mediator of DNA damage checkpoint 1 (MDC1) has been identified as a critical upstream mediator in the cellular response to DNA damage, however, some non-DNA damage responsive functions of MDC1 haven't been fully defined. In this study, we have identified MDC1 as a co-activator of ERα in breast cancer cells and demonstrated that MDC1 associates with ERα. MDC1 was also recruited to estrogen response element (ERE) of ERα target gene. Knockdown of MDC1 reduced the transcription of the endogenous ERα target genes, including p21. MDC1 depletion led to the promotion of breast cancer progression, and the expression of MDC1 is lower in breast cancer. Taken together, these results suggested that MDC1 was involved in the enhancement of ERα-mediated transactivation in breast cancer cells. This positive regulation by MDC1 might contribute to the suppression of breast cancer progression by acting as a barrier of positive to negative ERα function transformation.
authors.affiliation: 1. Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, and Key laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Renlong
authors.initials: R
authors.lastname: Zou
authors.affiliation: 2. Department of General Surgery, the First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, China.
authors.forename: Xinping
authors.initials: X
authors.lastname: Zhong
authors.affiliation: 1. Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, and Key laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Wang
authors.affiliation: 1. Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, and Key laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Hongmiao
authors.initials: H
authors.lastname: Sun
authors.affiliation: 1. Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, and Key laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Wang
authors.affiliation: 1. Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, and Key laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: 1. Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, and Key laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Shiying
authors.initials: S
authors.lastname: Sun
authors.affiliation: 1. Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, and Key laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Changci
authors.initials: C
authors.lastname: Tong
authors.affiliation: 1. Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, and Key laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Luo
authors.affiliation: 1. Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, and Key laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.affiliation: 1. Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, and Key laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Yanshu
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1. Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, and Key laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: 3. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110003, China.
authors.forename: Da
authors.initials: D
authors.lastname: Li
authors.affiliation: 1. Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, and Key laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Cao
authors.affiliation: 1. Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, and Key laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047468:Immunoprecipitation; D061986:MCF-7 Cells; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C413163:MDC1 protein, human; D009687:Nuclear Proteins; D011960:Receptors, Estrogen; D015534:Trans-Activators
keywords: MDC1; breast cancer; co-activator; estrogen receptor α; tumor suppression