Cloning of laminin gamma2 cDNA and chromosome mapping of the genes for the dog adhesion ligand laminin 5.
Overexpression of the gamma2 chain of laminin-5 has been linked to tumor invasion and an unfavorable prognostic value, but the role of this adhesion molecule in cancer progression remains unclear. Because dog models of human cancers provide the opportunity of clarifying the relation between laminin-5 and tumor malignancy we have isolated and characterized the cDNA of dog gamma2 chain. Comparative analysis of the nucleotide sequence revealed high identity between the dog and the human gamma2, including the intermolecular molecule binding sites and the regulatory promoter sequences. Moreover, expression of a recombinant human gamma2 chain in dog keratinocytes results in assembly and secretion of hybrid laminin-5 molecules, which underscore the functional relevance of the gamma2 conserved domains. We have also determined the syntenic location of the dog laminin-5 loci on CFA7. Our study provides a basis for therapeutical approaches of epithelial cancers of gamma2 using dogs as large animal models.
Capt
Annabelle
A
INSERM U385, Faculté de Médécine, Nice Cedex 2, France.
Spirito
Flavia
F
Guyon
Richard
R
André
Catherine
C
Ortonne
Jean-Paul
JP
Meneguzzi
Guerrino
G
D000595:Amino Acid Sequence; D000818:Animals; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002874:Chromosome Mapping / Q000379:methods*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics*; D004285:Dogs; D020869:Gene Expression Profiling; D016678:Genome; D006801:Humans; D015603:Keratinocytes / Q000737:chemistry* / Q000378:metabolism*; D007797:Laminin / Q000235:genetics* / Q000378:metabolism*; D008024:Ligands; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D007797:Laminin; D008024:Ligands; D000097794:Kalinin; C400567:LAMC2 protein, human