title: Extracellular matrix-dependent tissue-specific gene expression in mammary epithelial cells requires both physical and biochemical signal transduction.
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.
authors.affiliation: Life Sciences Division, Lawrence Berkeley Laboratory, Berkeley, CA 94720.
authors.forename: C D
authors.initials: CD
authors.lastname: Roskelley
authors.forename: P Y
authors.initials: PY
authors.lastname: Desprez
authors.forename: M J
authors.initials: MJ
authors.lastname: Bissell
mesh_terms: D000818:Animals; D002364:Caseins / Q000378:metabolism*; D002449:Cell Aggregation; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D019833:Genistein; D066298:In Vitro Techniques; D016023:Integrins / Q000502:physiology*; D007529:Isoflavones / Q000494:pharmacology; D051379:Mice; D019000:Phosphotyrosine; D011388:Prolactin / Q000494:pharmacology*; D011940:Receptor Aggregation; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D002364:Caseins; D016023:Integrins; D007529:Isoflavones; D019000:Phosphotyrosine; D014443:Tyrosine; D011388:Prolactin; D019833:Genistein; D013755:Tetradecanoylphorbol Acetate