Laminin mediates tissue-specific gene expression in mammary epithelia.
Tissue-specific gene expression in mammary epithelium is dependent on the extracellular matrix as well as hormones. There is good evidence that the basement membrane provides signals for regulating beta-casein expression, and that integrins are involved in this process. Here, we demonstrate that in the presence of lactogenic hormones, laminin can direct expression of the beta-casein gene. Mouse mammary epithelial cells plated on gels of native laminin or laminin-entactin undergo functional differentiation. On tissue culture plastic, mammary cells respond to soluble basement membrane or purified laminin, but not other extracellular matrix components, by synthesizing beta-casein. In mammary cells transfected with chloramphenicol acetyl transferase reporter constructs, laminin activates transcription from the beta-casein promoter through a specific enhancer element. The inductive effect of laminin on casein expression was specifically blocked by the E3 fragment of the carboxy terminal region of the alpha 1 chain of laminin, by antisera raised against the E3 fragment, and by a peptide corresponding to a sequence within this region. Our results demonstrate that laminin can direct tissue-specific gene expression in epithelial cells through its globular domain.
Streuli
C H
CH
School of Biological Sciences, University of Manchester, Zürich.
Schmidhauser
C
C
Bailey
N
N
Yurchenco
P
P
Skubitz
A P
AP
Roskelley
C
C
Bissell
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D002364:Caseins / Q000096:biosynthesis / Q000235:genetics; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D046508:Culture Techniques / Q000379:methods; D004848:Epithelium / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D008894:Milk Proteins / Q000096:biosynthesis; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic
D002364:Caseins; D007797:Laminin; D008894:Milk Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D015500:Chloramphenicol O-Acetyltransferase