Laminin-5 promotes adhesion and migration of epithelial cells: identification of a migration-related element in the γ2 chain gene (LAMC2) with activity in transgenic mice1Sirpa Salo and Heli Haakana contributed equally to this study.1
pmid: 10372560
Laminin-5 promotes adhesion and migration of epithelial cells: identification of a migration-related element in the γ2 chain gene (LAMC2) with activity in transgenic mice1Sirpa Salo and Heli Haakana contributed equally to this study.1
The effects of laminin-5 and its subunit gamma2 chain on cell adhesion and migration were studied, and a migration-related cis-acting element was identified in the gamma2 chain gene (LAMC2) using promoter-reporter gene constructs in transgenic mice. Intact laminin-5 molecules, but not recombinant gamma2 chain promoted cell adhesion of human keratinocytes and mouse squamous carcinoma cells, indicating that the gamma2 chain does not contain a cellular binding site. However, the gamma2 chain as such is probably involved in the process of cell locomotion, as antibodies against the short arm of the chain inhibited migration of carcinoma cells in an in vitro assay. Further evidence for the involvement of the gamma2 chain in cell migration was obtained by the identification of a cis-acting element in a promoter-lacZ reporter gene construct that was active in migratory epithelial cells of healing wounds in mice made transgenic by microinjection of the construct into fertilized oozytes. The migration active element was located in the sequence between -613 and +55. The same construct, and another one containing 5900 base pairs of the 5' flanking region, yielded very limited expression in cells of normal tissues. The limited expression was, however, only observed in epithelial cells of different tissues, i.e. cell types that normally express laminin-5 in vivo. The results show that the sequence between -613 and +55 contains elements that can drive expression during epithelial cell migration and that also partially confers more general epithelium expression. However, elements outside -5900 and +55 are needed for normal epithelium expression of the LAMC2 gene.
- University of Copenhagen Denmark
- University of Copenhagen Denmark
- University of Oulu Finland
- Karolinska Institute Sweden
- Oulu University Hospital Finland
DNA, Complementary, Recombinant Fusion Proteins, Molecular Sequence Data, Gene Expression, Mice, Transgenic, Inbred C57BL, Transgenic, Cell Line, Promoter Regions, Mice, Genetic, Cell Movement, Genes, Reporter, Complementary, Cell Adhesion, Epithelial Cells/physiology, Inbred DBA, Animals, Humans, Promoter Regions, Genetic, Reporter, Cultured, Binding Sites, Base Sequence, Epithelial Cells, DNA, Tumor Cells, Mice, Inbred C57BL, Genes, Mice, Inbred DBA, Kalinin, Recombinant Fusion Proteins/metabolism, Rabbits, Cell Adhesion Molecules/genetics, Cell Adhesion Molecules
DNA, Complementary, Recombinant Fusion Proteins, Molecular Sequence Data, Gene Expression, Mice, Transgenic, Inbred C57BL, Transgenic, Cell Line, Promoter Regions, Mice, Genetic, Cell Movement, Genes, Reporter, Complementary, Cell Adhesion, Epithelial Cells/physiology, Inbred DBA, Animals, Humans, Promoter Regions, Genetic, Reporter, Cultured, Binding Sites, Base Sequence, Epithelial Cells, DNA, Tumor Cells, Mice, Inbred C57BL, Genes, Mice, Inbred DBA, Kalinin, Recombinant Fusion Proteins/metabolism, Rabbits, Cell Adhesion Molecules/genetics, Cell Adhesion Molecules
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