Estrogen regulates JNK1 genomic localization to control gene expression and cell growth in breast cancer cells.

ABSTRACT: Steroid hormone and MAPK signaling pathways functionally intersect, but the molecular mechanisms of this cross talk are unclear. Here, we demonstrate a functional convergence of the estrogen and c-Jun N-terminal kinase 1 (JNK1) signaling pathways at the genomic level in breast cancer cells. We find that JNK1 binds to many promoters across the genome. Although most of the JNK1-binding sites are constitutive, a subset is estrogen regulated (either induced on inhibited). At the estrogen-induced sites, estrogen receptor (ER)? is required for the binding of JNK1 by promoting its recruitment to estrogen response elements or other classes of DNA elements through a tethering mechanism, which in some cases involves activating protein-1. At estrogen-regulated promoters, JNK1 functions as a transcriptional coregulator of ER? in a manner that is dependent on its kinase activity. The convergence of ER? and JNK1 at target gene promoters regulates estrogen-dependent gene expression outcomes, as well as downstream estrogen-dependent cell growth responses. Analysis of existing gene expression profiles from breast cancer biopsies suggests a role for functional interplay between ER? and JNK1 in the progression and clinical outcome of breast cancers.

SUBMITTER: Sun M 

PROVIDER: S-EPMC3355551 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature