Transcriptomics

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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

SECONDARY ACCESSION(S): GSE30406PRJNA154829

REPOSITORIES: GEO, ArrayExpress

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