Steroid Hormones

Localizing Estrogen Receptor Signaling

Science's STKE  13 Aug 2002:
Vol. 2002, Issue 145, pp. tw295-TW295
DOI: 10.1126/stke.2002.145.tw295

Estrogen receptor (ER) signaling outside the nucleus is less well understood than are its direct effects on gene expression within the nucleus. Kumar et al. report that a balance between ER-mediated signaling in these distinct subcellular regions may be a crucial determinant of cellular responses to ER agonists. A shorter variant of metastatic tumor antigen 1 (MTA1s) that localizes to the cytoplasm of breast cancer cells was found to interact with ER through an ER-binding motif. This interaction resulted in sequestration of ER in the cytoplasm. When MTA1s was overexpressed in breast cancer cells, ER did not relocalize to the nucleus in response to estradiol. MTA1s-expressing cells also exhibited increased activation of the mitogen-activated kinase (MAPK) pathway, displayed anchorage-independent growth, and were more tumorigenic in mice. MTA1s may function to redirect ER signaling by blocking nuclear signaling and enhancing non-genomic functions in the cytoplasm. For more on non-genomic actions of steroid hormone receptors, see Cato et al.

R. Kumar, R.-A. Wang, A. Mazumdar, A. H. Talukder, M. Mandal, Z. Yang, R. Bagheri-Yarmand, A. Sahin, G. Hortobagyi, L. Adam, C. J. Barnes, R. K. Vadlamudi, A naturally occurring MTA1 variant sequesters oestrogen receptor-alpha in the cytoplasm. Nature 418, 654-657 (2002). [Online Journal]

A. C. B. Cato, A. Nestl, S. Mink, Rapid actions of steroid receptors in cellular signaling pathways. Science's STKE (2002),;2002/138/re9. [Abstract] [Full Text]