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doi: 10.1242/10.1242/jcs.00523
Research Article |
expression and function in mouse mammary epithelial cells
1 Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA
94720, USA
2 Department of Anatomy, University of British Columbia, Vancouver, British
Columbia, V6T 1Z3, Canada
* Author for correspondence (e-mail: mjbissell{at}lbl.gov)
Accepted 31 March 2003
The expression level and functional activity of estrogen receptor 
is an important determinant of breast physiology and breast cancer treatment.
However, it has been difficult to identify the signals that regulate estrogen
receptor because cultured mammary epithelial cells generally do not respond to
estrogenic signals. Here, we use a combination of two- and three-dimensional
culture systems to dissect the extracellular signals that control endogenous
estrogen receptor . Its expression was greatly reduced when primary
mammary epithelial cells were placed on tissue culture plastic; however, the
presence of a reconstituted basement membrane in combination with lactogenic
hormones partially prevented this decrease. Estrogen receptor
expression in primary mammary fibroblasts was not altered by these culture
conditions, indicating that its regulation is cell type specific. Moreover,
estrogen receptor-dependent reporter gene expression, as well as estrogen
receptor levels, were increased threefold in a functionally normal
mammary epithelial cell line when reconstituted basement membrane was added to
the medium. This regulatory effect of reconstituted basement membrane was
reproduced by two of its components, collagen-IV and laminin-1, and it was
blocked by antibodies against 2, 6 and ß1 integrin
subunits. Our results indicate that integrin-mediated response to specific
basement membrane components, rather than cell rounding or cell growth arrest
induced by reconstituted basement membrane, is critical in the regulation of
estrogen receptor expression and function in mammary epithelial
cells.
Key words: Basement membrane, Extracellular matrix, Mammary fibroblasts, Integrins
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