GSE107924 Transition of breast cancer cells from luminal to basal-like phenotype engages a shift from genomic to non-genomic activities of ER α activity

Contributors : Tamara Fernandez-Calero ; Charly Jehanno ; Denis Habauzit ; Stephane Avner ; Frederic Percevault ; Noureddine Boujrad ; Pascale Le Goff ; Monica Marin ; Denis Michel ; Rapha ël Métivier ; Gilles FlouriotSeries Type : Expression profiling by arrayOrganism : Homo sapiensEstrogen receptor (ER α) is central in driving the development of hormone-dependent breast cancers. A major challenge in treating these cancers is to understand and struggle endocrine resistance. We have previously shown that the Megakaryoblastic Leukemia 1 (MKL1) protein, a master regulator of actin dynamic and cellula r motile functions, directs down-regulation of ERα and hormonal escape of estrogen-responsive breast cancer cell lines. In the present study, we decipher the underlining mechanisms by tracking functional changes in ERα activity. We demonstrate through gene expression microarray analysis that the c onstitutive activation of MKL1 in ERα-positive MCF7 breast cancer cells induces a transition from a luminal to a basal-like phenotype and suppresses almost all regulations of gene expression by estrogen. Chromatin immunoprecipitation of DNA coupled to high-throughput sequencing (ChIP-Seq) shows a p rofound reprogramming in ERα cistrome associated with a massive loss of ERα binding sites (ERBSs) generally associated with lower ERα-binding activity. Novel ERBSs appear to be associated with EGF and RAS signaling pathways. ERα dynamic was further impacted by a displacemen...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research