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PMID: 7528920 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Extracellular matrix-dependent tissue-specific gene expression in mammary epithelial cells requires both physical and biochemical signal transduction.

Roskelley CD, Desprez PY, Bissell MJ

Abstract

Extracellular matrix (ECM) profoundly influences the growth and differentiation of the mammary gland epithelium, both in culture and in vivo. Utilizing a clonal population of mouse mammary epithelial cells that absolutely requires an exogenous ECM for function, we developed a rapid assay to study signal transduction by ECM. Two components of the cellular response to a basement membrane overlay that result in the expression of the milk protein beta-casein were defined. The first component of this response involves a rounding and clustering of the cells that can be physically mimicked by plating the cells on a nonadhesive substratum. The second component is biochemical in nature, and it is associated with beta 1 integrin clustering and increased tyrosine phosphorylation. The second component is initiated in a morphology-independent manner, but the proper translation of this biochemical signal into a functional response requires cell rounding and cell clustering. Thus, physical and biochemical signal transduction events contribute to the ECM-dependent regulation of tissue-specific gene expression in mouse mammary epithelial cells.

MeSH Terms
Animals Caseins/metabolism Cell Aggregation Cells, Cultured Extracellular Matrix/physiology Female Gene Expression Regulation, Developmental Genistein In Vitro Techniques Integrins/physiology Isoflavones/pharmacology Mice Phosphotyrosine Prolactin/pharmacology Receptor Aggregation Signal Transduction Tetradecanoylphorbol Acetate/pharmacology Time Factors Tyrosine/analogs & derivatives,metabolism
Chemicals
Caseins Integrins Isoflavones Phosphotyrosine Tyrosine Prolactin Genistein Tetradecanoylphorbol Acetate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Roskelley C D
Life Sciences Division, Lawrence Berkeley Laboratory, Berkeley, CA 94720.
Desprez P Y
Bissell M J
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42 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1994-12-20
Pages
12378-82
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC45441
Subset
IM
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