PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer

ABSTRACT: Activating mutations of PIK3CA are the most frequent genomic alterations in estrogen receptor (ER)-positive breast tumors and selective PI3Kα inhibitors are in clinical development. The activity of these agents, however, is not homogenous and only a fraction of patients bearing PIK3CA-mutant ER-positive tumors benefit from single agent administration. Searching for mechanisms of resistance, we observed that suppression of PI3K signaling with different agents results in induction of ER-dependent transcriptional activity as demonstrated by changes in expression in genes containing ER binding sites, enhanced ER transcription and increased occupancy by the ER of promoter regions of upregulated genes. Furthermore, expression of ESR1 mRNA and ER protein levels themselves were also increased upon

ORGANISM(S): Homo sapiens

SUBMITTER: Aleix Prat 

PROVIDER: E-GEOD-64033 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress