title: Activin A inhibits vascular endothelial cell growth and suppresses tumour angiogenesis in gastric cancer.
abstract: BACKGROUND
  Activin A is a multi-functional cytokine belonging to the transforming growth factor-β (TGF-β) superfamily; however, the effect of activin A on angiogenesis remains largely unclear. We found that inhibin β A subunit (INHBA) mRNA is overexpressed in gastric cancer (GC) specimens and investigated the effect of activin A, a homodimer of INHBA, on angiogenesis in GC.
  
  
  METHODS
  Anti-angiogenic effects of activin A via p21 induction were evaluated using human umbilical vein endothelial cells (HUVECs) in vitro and a stable INHBA-introduced GC cell line in vivo.
  
  
  RESULTS
  Compared with TGF-β, activin A potently inhibited the cellular proliferation and tube formation of HUVECs with induction of p21. A promoter assay and a chromatin immunoprecipitation assay revealed that activin A directly regulates p21 transcriptional activity through Smads. Stable p21-knockdown significantly enhanced the cellular proliferation of HUVECs. Notably, stable p21-knockdown exhibited a resistance to activin-mediated growth inhibition in HUVECs, indicating that p21 induction has a key role on activin A-mediated growth inhibition in vascular endothelial cells. Finally, a stable INHBA-introduced GC cell line exhibited a decrease in tumour growth and angiogenesis in vivo.
  
  
  CONCLUSIONS
  Our findings highlight the suppressive role of activin A, unlike TGF-β, on tumour growth and angiogenesis in GC.
authors: Department of Genome Biology, Kinki University School of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan.
authors: H
authors: H
authors: Kaneda
authors: T
authors: T
authors: Arao
authors: K
authors: K
authors: Matsumoto
authors: M A
authors: MA
authors: De Velasco
authors: D
authors: D
authors: Tamura
authors: K
authors: K
authors: Aomatsu
authors: K
authors: K
authors: Kudo
authors: K
authors: K
authors: Sakai
authors: T
authors: T
authors: Nagai
authors: Y
authors: Y
authors: Fujita
authors: K
authors: K
authors: Tanaka
authors: K
authors: K
authors: Yanagihara
authors: Y
authors: Y
authors: Yamada
authors: I
authors: I
authors: Okamoto
authors: K
authors: K
authors: Nakagawa
authors: K
authors: K
authors: Nishio
mesh_terms: D028341:Activins / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010766:Phosphorylation; D051899:Smad2 Protein / Q000378:metabolism; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017931:DNA Primers; D051899:Smad2 Protein; D042461:Vascular Endothelial Growth Factor A; C422405:activin A; D028341:Activins