Discovery of NM23-H2 as an estrogen receptor beta-associated protein: role in estrogen-induced gene transcription and cell migration.
The regulation of the estrogenic responses may be influenced by the proteins that associate with estrogen receptors (ERs) rather than solely with the receptors themselves. ERbeta is expressed in blood vessels and may play an important role in vascular disease. We hypothesized that specific proteins interact with ERbeta to modulate its response to estrogens. By means of a yeast two hybrid screen, we discovered that NM23-H2, a multi-faceted protein associates specifically with ERbeta. NM23-H2 and ERbeta consistently co-localize in a variety of human tissues (e.g. breast tissue), whereas ERalpha and NM23-H2 did not co-localize. Estrogen response element-mediated transcription increased by 97% when NM23-H2 and ERbeta were over-expressed in MCF-7 cells (p< or =0.001). Moreover, there was a synergistic effect of NM23-H2 over-expression with estrogen treatment on the reduction of MCF-7 cell migration (p< or =0.001). These results suggest that NM23-H2 associates with ERbeta and is capable of modulating estrogen-induced gene transcription, as well as cell migration. Hence, NM23-H2 may play an important role in modulating the response to endogenous and exogenous estrogens, perhaps even within the context of vascular disease.
Rayner
Katey
K
Vascular Biology Laboratory, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Chen
Yong-Xiang
YX
Hibbert
Benjamin
B
White
Dawn
D
Miller
Harvey
H
Postel
Edith H
EH
O'Brien
Edward R
ER
D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D054778:NM23 Nucleoside Diphosphate Kinases / Q000378:metabolism*; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured
D047629:Estrogen Receptor beta; D004967:Estrogens; D054778:NM23 Nucleoside Diphosphate Kinases