Nidogen-1 regulates laminin-1-dependent mammary-specific gene expression

Journal Article · Tue Feb 01 04:00:00 EST 2000 · Journal of Cell Science

OSTI ID:771755

Pujuguet, Philippe ^[1]; Simian, Marina; Liaw, Jane; Timpl, Rupert; Werb, Zena; Bissell, Mina J

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1. LBNL Library

Nidogen-1 (entactin) acts as a bridge between the extracellular matrix molecules laminin-1 and type IV collagen, and thus participates in the assembly of basement membranes. To investigate the role of nidogen-1 in regulating cell-type-specific gene expression in mammary epithelium, we designed a culture microecosystem in which each component, including epithelial cells, mesenchymal cells, lactogenic hormones and extracellular matrix, could be controlled. We found that primary and established mesenchymal and myoepithelial cells synthesized and secreted nidogen-1, whereas expression was absent in primary and established epithelial cells. In an epithelial cell line containing mesenchymal cells, nidogen-1 was produced by the mesenchymal cells but deposited between the epithelial cells. In this mixed culture, mammary epithelial cells express b-casein in the presence of lactogenic hormones. Addition of either laminin-1 plus nidogen-1, or laminin-1 alone to mammary epithelial cells induced b- casein production. We asked whether recombinant nidogen-1 alone could signal directly for b-casein. Nidogen-1 did not induce b-casein synthesis in epithelial cells, but it augmented the inductive capacity of laminin-1. These data suggest that nidogen-1 can cooperate with laminin-1 to regulate b-casein expression. Addition of full length nidogen-1 to the mixed cultures had no effect on b-casein gene expression; however, a nidogen-1 fragment containing the laminin-1 binding domain, but lacking the type IV collagen-binding domain, had a dominant negative effect on b-casein expression. These data point to a physiological role for nidogen-1 in the basement membrane-induced gene expression by epithelial cells.

• Research Organization: Lawrence Berkeley National Lab., CA (US)
• Sponsoring Organization: USDOE Director, Office of Science. Office of Biological and Environmental Research; National Institutes of Health (US)
• DOE Contract Number: AC03-76SF00098
• OSTI ID: 771755
• Report Number(s): LBNL--44571
• Journal Information: Journal of Cell Science, Journal Name: Journal of Cell Science Journal Issue: 5 Vol. 113; ISSN 0021-9533; ISSN JNCSAI
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BASEMENTS
CAPACITY
CASEIN
COLLAGEN
EPITHELIUM
GENES
HORMONES
MEMBRANES
NIDOGEN-1 ENTACTIN BASEMENT MEMBRANE EXTRACELLULAR MATRIX TISSUE-SPECIFIC GENE EXPRESSION EPITHELIAL-MESENCHYMAL INTERACTION S MAMMARY GLAND
PRODUCTION
SYNTHESIS