Discovery of NM23-H2 as an estrogen receptor β-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. ERβ is expressed in blood vessels and may play an important role in vascular disease. We hypothesized that specific proteins interact with ERβ 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 ERβ. NM23-H2 and ERβ consistently co-localize in a variety of human tissues (e.g. breast tissue), whereas ERα and NM23-H2 did not co-localize. Estrogen response element-mediated transcription increased by 97% when NM23-H2 and ERβ were over-expressed in MCF-7 cells (p ≤ 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 ≤ 0.001). These results suggest that NM23-H2 associates with ERβ 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.