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MED1 (mediator subunit 1) co-amplifies with HER2, but its role in HER2-driven mammary tumorigenesis is still unknown. Here, we generate MED1 mammary-specific overexpression mice and cross them with mouse mammary tumor virus (MMTV)-HER2 mice. We observe significantly promoted onset, growth, metastasis, and multiplicity of HER2 tumors by MED1 overexpression. Further studies reveal critical roles for MED1 in epithelial-mesenchymal transition, cancer stem cell formation, and response to anti-HER2 therapy. Mechanistically, RNA sequencing (RNA-seq) transcriptome analyses and clinical sample correlation studies identify Jab1, a component of the COP9 signalosome complex, as the key direct target gene of MED1 contributing to these processes. Further studies reveal that Jab1 can also reciprocally regulate the stability and transcriptional activity of MED1. Together, our findings support a functional cooperation between these co-amplified genes in HER2+ mammary tumorigenesis and their potential usage as therapeutic targets for the treatment of HER2+ breast cancers.
Pubmed ID: 33691110
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A collection of tools for flow cytometer and application setup, data acquisition, and data analysis that help streamline flow cytometry workflows. It provides features to help users integrate flow systems into new application areas, including index sorting for stem cell and single-cell applications, as well as automation protocols for high-throughput and robotic laboratories.
View all literature mentionsSoftware that estimates expression at transcript-level resolution and controls for variability evident across replicate libraries.
View all literature mentionsGlobal nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsNon-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsSoftware tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.
View all literature mentionsSoftware tool for transcriptome assembly and differential expression analysis for RNA-Seq. Includes script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.
View all literature mentionsSoftware tool for limiting dilution analysis, with particular attention to needs of stem cell assays. Provides confidence intervals for all LDA data sets, including those with 0% or 100% responses. Other features include test of adequacy of single hit hypothesis, tests for frequency differences between multiple data sets, and ability to take advantage of cases where number of cells in sample is counted exactly.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets CD31
View all literature mentionsThis monoclonal targets CD29
View all literature mentionsThis monoclonal targets CD326
View all literature mentionsThis polyclonal targets ERα
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis monoclonal targets Monoclonal antibodies are produced by immunizing rabbits with a synthetic phosphopeptide (KLH-coupled) corresponding to residues surrounding tyrosines 1221/1222 of human ErbB2 protein.
View all literature mentionsThis polyclonal targets E Cadherin
View all literature mentionsThis monoclonal targets Cdkn1b
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis monoclonal targets TER-119/Erythroid cells
View all literature mentionsThis monoclonal targets Pan Cytokeratin
View all literature mentionsThis monoclonal targets EVL (G-8)
View all literature mentionsThis polyclonal targets N Cadherin
View all literature mentionsThis monoclonal targets HER2/ErbB2 (29D8) Rabbit mAb
View all literature mentionsThis monoclonal targets Vimentin antibody [EPR3776]
View all literature mentionsThis monoclonal targets Timeless
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis recombinant monoclonal targets Ki-67
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsCell line SK-BR-3 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-7 Tam1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BT-474 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name FVB/N-Tg(MMTVneu)202Mul/J from IMSR.
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