An anti-proliferative gene BTG1 regulates angiogenesis in vitro.
B-cell translocation gene 1 (BTG1) is a member of the anti-proliferative gene family that regulates cell growth and differentiation. To clarify the role of BTG1 in angiogenesis, we examined the regulation of BTG1 expression in cultured endothelial cells and characterized its function in in vitro models of angiogenesis. BTG1 mRNA was abundantly expressed in quiescent endothelial cells. Addition of serum and angiogenic growth factors decreased BTG1 mRNA levels in endothelial cells. In contrast, BTG1 mRNA was up-regulated in tube-forming endothelial cells on Matrigel. This up-regulation was partially blocked by neutralizing antibody against transforming growth factor-beta (TGF-beta), and TGF-beta increased BTG1 mRNA levels. Inhibition of endogenous BTG1 by overexpression of antisense BTG1 resulted in inhibited network formation, and overexpression of sense BTG1 augmented tube formation in these cell lines. BTG1-overexpressing endothelial cells displayed increased cell migration. These findings suggest that BTG1 may play an important role in the process of angiogenesis.
Iwai
Kenji
K
Division of Cardiovascular and Respiratory Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Hirata
Ken-ichi
K
Ishida
Tatsuro
T
Takeuchi
Shigeto
S
Hirase
Tetsuaki
T
Rikitake
Yoshiyuki
Y
Kojima
Yoko
Y
Inoue
Nobutaka
N
Kawashima
Seinosuke
S
Yokoyama
Mitsuhiro
M
D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D002448:Cell Adhesion; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D015536:Down-Regulation; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D066298:In Vitro Techniques; D007797:Laminin / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000502:physiology*; D009389:Neovascularization, Pathologic; D009841:Oligonucleotides / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011509:Proteoglycans / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
D004338:Drug Combinations; D007797:Laminin; D009363:Neoplasm Proteins; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D011509:Proteoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C059485:matrigel; C074086:BTG1 protein, human; D003094:Collagen