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E-GEOD-31870 - Maintenance of Hormone Responsiveness in Luminal Breast Cancers by Suppression of Notch

Status
Released on 21 December 2011, last updated on 2 May 2014
Organism
Homo sapiens
Samples (48)
Array (1)
Protocols (55)
Description
Luminal breast cancers express estrogen (ER) and/or progesterone (PR) receptors and respond to hormone therapies. Basal-like “triple negative” (TN) cancers lack steroid receptors but are cytokeratin (CK) 5-positive and require chemotherapy. Here we show that over half of primary ER+PR+ breast cancers contain an ER–PR–CK5+ “luminobasal” subpopulation exceeding 1% of cells. Starting from ER+PR+ luminal cell lines, we generated novel lines with varying luminal to luminobasal-cell ratios and studied their molecular and biological properties. In luminal disease, luminobasal cells expand in response to antiestrogen or estrogen withdrawal therapies. The phenotype and gene signature of the hormone resistant cells matches that of clinical TN basal-like and claudin-low disease. Luminobasal-cell expansion in response to hormone therapies is regulated by Notch1 signaling and can be blocked by gamma-secretase inhibitors (GSI). Our data establish a previously unrecognized plasticity of ER+PR+ luminal breast cancers that, without genetic manipulation, mobilizes outgrowth of hormone-resistant basal-like disease in response to treatment. This undesirable outcome can be prevented by combining endocrine therapies with Notch inhibition. 24 array samples
Experiment type
transcription profiling by array 
Contacts
Charles Perou <cperou@med.unc.edu>, Charles M Perou, James M Haughian, Kathryn B Horwitza
Citation
Maintenance of hormone responsiveness in luminal breast cancers by suppression of Notch. Haughian JM, Pinto MP, Harrell JC, Bliesner BS, Joensuu KM, Dye WW, Sartorius CA, Tan AC, Heikkilä P, Perou CM, Horwitz KB. , PMID:21969591
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-31870.idf.txt
Sample and data relationshipE-GEOD-31870.sdrf.txt
Processed data (1)E-GEOD-31870.processed.1.zip
Array designA-GEOD-10481.adf.txt
Links