TY - JOUR
T1 - Estrogen regulates JNK1 genomic localization to control gene expression and cell growth in breast cancer cells
AU - Sun, Miao
AU - Isaacs, Gary D.
AU - Hah, Nasun
AU - Heldring, Nina
AU - Fogarty, Elizabeth A.
AU - Lee Kraus, W.
PY - 2012/5
Y1 - 2012/5
N2 - 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.Wefind 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 ERα 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 ERα and JNK1 in the progression and clinical outcome of breast cancers.
AB - 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.Wefind 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 ERα 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 ERα and JNK1 in the progression and clinical outcome of breast cancers.
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U2 - 10.1210/me.2011-1158
DO - 10.1210/me.2011-1158
M3 - Article
C2 - 22446103
AN - SCOPUS:84860332427
SN - 0888-8809
VL - 26
SP - 736
EP - 747
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 5
ER -