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The ets transcription factor ELF5 suppresses the estrogen sensitive phenotype and contributes to antiestrogen resistance in luminal breast cancer. [mouse]

ABSTRACT: The ets transcription factor ELF5 specifies the differentiation of mammary progenitor cells to establish the milk-secreting lineage. ER- and poor prognosis basal breast cancers arise from this progenitor cell and these cancers express high levels of Elf5. Knockdown of ELF5 expression in basal breast cancer cell lines, or forced expression in luminal breast cancer cell lines, resulted in reduced cell proliferation. Transcript profiling and chromatin immunoprecipitation revealed that the transcriptional activity of ELF5 specified the gene expression patterns that distinguish basal from luminal breast cancer, including suppression of FOXA1, GATA3 and ER, key estrogen-action genes. Tamoxifen treatment of luminal MCF7 cells upregulated Elf5 expression and cells that acquired resistance to Tamoxifen became dependent on ELF5 for proliferation. ELF5 is a regulator of breast cancer cell proliferation, transcriptionally specifies the basal molecular subtype and is utilised by ER+ breast cancer cells to escape proliferative arrest caused by Tamoxifen. Elf5 was induced via doxycycline treated PyMT mouse tumours, in triplicate

ORGANISM(S): Mus musculus  

SUBMITTER: Alex Swarbrick  Maria Kalyuga   David Gallego-Ortega   Robert I Nicholson   Tilman Brummer   Liz Caldon   Mark Cowley   Rosalind Launchbury   Susan J Clark   Aaron L Statham   Matthew J Naylor   Andrea Egger   Adelaide Young   Fatima Valdes-Mora   Nicola Armstrong   Stephanie L Allerdice   M C Alles   Julia M Gee   Mark J Cowley   Robert L Sutherland   Cara J Evans   Wendy Au   Catherine L Piggin   Christopher J Ormandy   Andrew Stone   Jason S Carroll   Heather J Lee   Warren Kaplan    

PROVIDER: E-GEOD-30406 | ArrayExpress | 2014-01-13



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