Collagen-IV and laminin-1 regulate estrogen receptor alpha expression and function in mouse mammary epithelial cells.

Abstract:

:The expression level and functional activity of estrogen receptor alpha 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 alpha. 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 alpha 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 alpha 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 alpha2, alpha6 and beta1 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 alpha expression and function in mammary epithelial cells.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Novaro V,Roskelley CD,Bissell MJ

doi

10.1242/jcs.00523

keywords:

subject

Has Abstract

pub_date

2003-07-15 00:00:00

pages

2975-86

issue

Pt 14

eissn

0021-9533

issn

1477-9137

pii

116/14/2975

journal_volume

116

pub_type

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