title: Thymosin β4 induces the expression of vascular endothelial growth factor (VEGF) in a hypoxia-inducible factor (HIF)-1α-dependent manner.
abstract: 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.
authors.affiliation: Department of Parasitology and Genetics, Kosin University College of Medicine, Busan, Republic of Korea.
authors.forename: Jin-Ok
authors.initials: JO
authors.lastname: Jo
authors.forename: Su-Ryun
authors.initials: SR
authors.lastname: Kim
authors.forename: Moon-Kyung
authors.initials: MK
authors.lastname: Bae
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Kang
authors.forename: Mee Sun
authors.initials: MS
authors.lastname: Ock
authors.forename: Hynda K
authors.initials: HK
authors.lastname: Kleinman
authors.forename: Hee-Jae
authors.initials: HJ
authors.lastname: Cha
mesh_terms: 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)
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008156:Luciferases; D012333:RNA, Messenger; D013947:Thymosin; D042461:Vascular Endothelial Growth Factor A; D000099201:Thymosin beta(4)