Thymosin β4 induces the expression of vascular endothelial growth factor (VEGF) in a hypoxia-inducible factor (HIF)-1α-dependent manner.
Thymosin β4 has multi-functional roles in cell physiology, but little is known about its mechanism(s) of action. We previously reported that thymosin β4 stimulated angiogenesis through the induction of vascular endothelial growth factor (VEGF). To identify the mechanism of VEGF induction by thymosin β4, we have used a luciferase assay system with VEGF in the 5' promoter region. We also analyzed the effect of thymosin β4 on VEGF mRNA stability and on the expression and stability of hypoxia-inducible factor (HIF)-1α. We found that thymosin β4 induces VEGF expression by an increase in the stability of HIF-1α protein. Analysis of the expression patterns of thymosin β4 and HIF-1α in colon cancer tissue microarray showed that thymosin β4 and HIF-1α co-localized in these biopsies. These data show that thymosin β4 induces the expression of VEGF indirectly by increasing the protein stability of HIF-1α.
Jo
Jin-Ok
JO
Department of Parasitology and Genetics, Kosin University College of Medicine, Busan, Republic of Korea.
Kim
Su-Ryun
SR
Bae
Moon-Kyung
MK
Kang
Yun-Jeong
YJ
Ock
Mee Sun
MS
Kleinman
Hynda K
HK
Cha
Hee-Jae
HJ
D000818:Animals; D001706:Biopsy; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D011401:Promoter Regions, Genetic / Q000235:genetics; D055550:Protein Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013947:Thymosin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D046888:Tissue Array Analysis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D000099201:Thymosin beta(4)
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008156:Luciferases; D012333:RNA, Messenger; D013947:Thymosin; D042461:Vascular Endothelial Growth Factor A; D000099201:Thymosin beta(4)