The human mammary gland basement membrane is integral to the polarity of luminal epithelial cells.
We show that myoepithelial cell basement membrane derived E3 and E8 domains of laminin-1 are capable of polarizing luminal epithelial cells with regard to epithelial membrane antigen localization. This event is dependent on the alpha6 integrin and results in aggregation and phosphorylation of the tyrosine residues of the focal adhesion kinase complex. We also demonstrate that uncultured normal luminal epithelial cells synthesize normal levels of beta and gamma laminin chains and reduced levels of alpha chains mRNA in common with malignant epithelial cells. In contrast normal myoepithelial cells synthesize all three constituent chains of laminin-1. Therefore in breast cancer the absence of myoepithelial cells could result in a lack of laminin alpha chains which may contribute to loss of polarity of malignant epithelial cells.
Department of Cancer Medicine, Imperial College School of Medicine, Charing Cross Campus, St. Dunstan's Road, London, W6 8RP, England. m.slade@cxwms.ac.uk
M J
MJ
Slade
R C
RC
Coope
J J
JJ
Gomm
R C
RC
Coombes
D000595:Amino Acid Sequence; D001485:Basement Membrane / Q000473:pathology / Q000502:physiology; D001940:Breast / Q000166:cytology* / Q000473:pathology / Q000502:physiology; D001943:Breast Neoplasms; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D007797:Laminin / Q000096:biosynthesis; D008969:Molecular Sequence Data; D014407:Tumor Cells, Cultured
D007797:Laminin