title: Dynamic regulation of gene expression by the Flt-1 kinase and Matrigel in endothelial tubulogenesis.
abstract: A nontubulogenic endothelial cell line, NP31, can be transformed by the active form of the Flt-1 kinase (BCR-FLTm1) into Tb3 cells, which show a tubulogenic property only when cultured in Matrigel. By utilizing this strict dependence of NP31 on BCR-FLTm1 and Matrigel for experimental angiogenesis, we performed microarray analyses under several conditions and found 97 genes whose dynamically regulated profiles of gene expression are divided into nine groups, in two major clusters. In one major cluster, gene expression is interdependently regulated by BCR-FLTm1 or Matrigel. The second major cluster contains genes whose expression patterns under BCR-FLTm1 influence are reversed by Matrigel. Based on these gene expression patterns in NP31 driven by BCR-FLTm1 and/or Matrigel, we propose a model in which sequential and alternate stimulation by BCR-FLTm1 and Matrigel induces cooperative regulation of subsets of genes. Microarray analyses of Tb3 under 11 different conditions revealed 5 candidate genes whose gene expression regulation is most closely associated with tubulogenesis.
authors.affiliation: Division of Genetics, The Institute of Medical Science, University of Tokyo, Japan.
authors.forename: Satsuki
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Emi
authors.initials: E
authors.lastname: Ito
authors.forename: Reiko
authors.initials: R
authors.lastname: Honma
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
authors.forename: Masabumi
authors.initials: M
authors.lastname: Shibuya
authors.forename: Shinya
authors.initials: S
authors.lastname: Watanabe
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Maru
mesh_terms: D000818:Animals; D002460:Cell Line; D003094:Collagen; D004338:Drug Combinations; D042783:Endothelial Cells / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D007797:Laminin; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D011509:Proteoglycans; D051381:Rats; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D040281:Vascular Endothelial Growth Factor Receptor-1