Estrogen receptor α (ERα) 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 ERα 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 ERα 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 ERα expression/activity in a cultured cell line and inhibits the loss of ERα 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 α2,α6 and β1 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.