Journal of Cell Science 116, e1403 (2003)
Copyright © 2003 The Company of Biologists Limited
Dissecting estrogen receptor regulation
Estrogen receptor 
(ER) is a hormone-dependent
transcriptional regulator that mediates responses to estrogen during mammary
development, and its deregulation correlates with breast cancer progression.
Understanding the regulation of ER is an important goal but has been
hampered by the fact that cultured mammary epithelial cell monolayers fail to
respond to estrogen. Mina Bissell and co-workers have examined regulation of
ER in 2D and 3D culture systems that provide a better model of the in
vivo microenvironment (see p.
2975). They find that the introduction of reconstituted basement
membrane (which normally separates epithelial cells from the surrounding
stroma) stimulates ER expression/activity in a cultured cell line and
inhibits the loss of ER that accompanies transfer of primary mammary
epithelial cells to tissue culture. The authors go on to show that two
basement membrane components, collagen VI and laminin 1, can reproduce this
effect. Furthermore, they show that antibodies to the integrin 2,
6 and ß1 subunits block it. These findings thus not only
demonstrate the usefulness of the authors' approach for analysis of
context-dependent signalling but reveal that the effect of the basement
membrane is due to specific integrin-mediated interactions.
Related articles in JCS:
- Collagen-IV and laminin-1 regulate estrogen receptor expression and function in mouse mammary epithelial cells
- Virginia Novaro, Calvin D. Roskelley, and Mina J. Bissell
JCS 2003 116: 2975-2986.
[Abstract]
[Full Text]
