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Cancer Cell DOI:10.1016/j.ccr.2014.04.024

JARID1B is a luminal lineage-driving oncogene in breast cancer.

Publication TypeJournal Article
Year of Publication2014
AuthorsYamamoto, S, Wu, Z, Russnes, HG, Takagi, S, Peluffo, G, Vaske, C, Zhao, X, Vollan, HKristian M, Maruyama, R, Ekram, MB, Sun, H, Kim, JHyun, Carver, K, Zucca, M, Feng, J, Almendro, V, Bessarabova, M, Rueda, OM, Nikolsky, Y, Caldas, C, X Liu, S, Polyak, K
JournalCancer Cell
Volume25
Issue6
Pages762-77
Date Published2014 Jun 16
ISSN1878-3686
KeywordsBreast Neoplasms, Cell Growth Processes, Cell Line, Tumor, Cell Lineage, Female, Gene Amplification, Gene Expression Regulation, Neoplastic, Histones, Humans, Jumonji Domain-Containing Histone Demethylases, MCF-7 Cells, Mutation, Nuclear Proteins, Oncogenes, Promoter Regions, Genetic, Pyrazoles, Pyrroles, Repressor Proteins, RNA, Small Interfering, Transfection, Transforming Growth Factor beta
Abstract

Recurrent mutations in histone-modifying enzymes imply key roles in tumorigenesis, yet their functional relevance is largely unknown. Here, we show that JARID1B, encoding a histone H3 lysine 4 (H3K4) demethylase, is frequently amplified and overexpressed in luminal breast tumors and a somatic mutation in a basal-like breast cancer results in the gain of unique chromatin binding and luminal expression and splicing patterns. Downregulation of JARID1B in luminal cells induces basal genes expression and growth arrest, which is rescued by TGFβ pathway inhibitors. Integrated JARID1B chromatin binding, H3K4 methylation, and expression profiles suggest a key function for JARID1B in luminal cell-specific expression programs. High luminal JARID1B activity is associated with poor outcome in patients with hormone receptor-positive breast tumors.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S1535-6108(14)00186-X
DOI10.1016/j.ccr.2014.04.024
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24937458?dopt=Abstract

Alternate JournalCancer Cell
PubMed ID24937458
PubMed Central IDPMC4079039
Grant ListP01 CA080111 / CA / NCI NIH HHS / United States
R01 GM099409 / GM / NIGMS NIH HHS / United States
CA080111 / CA / NCI NIH HHS / United States
GM099409 / GM / NIGMS NIH HHS / United States