title: SV40 T/t-common polypeptide inhibits angiogenesis and growth of HER2-overexpressing human ovarian cancer.
abstract: Human epidermal growth factor receptor 2 (HER2) is frequently overexpressed in human ovarian cancers and its overexpression is associated with increased angiogenesis, increased metastasis and reduced survival. Inhibition of HER2 in HER2-overexpressing cancers can lead to reduced angiogenesis and improved survival. Previously, we reported that SV40 T/t-common polypeptide has transcriptional repression activity and can inhibit HER2 expression. In this study, we investigated the effect of T/t-common on the angiogenesis-inducing activity of HER2-overexpressing human SK-OV-3 ovarian cancer cells. We found that compared to conditioned medium from control SK-OV-3 cancer cells, conditioned medium from T/t-common-expressing SK-OV-3 cells had a reduced ability to induce endothelial cell migration and tube formation in vitro and microvessel formation in vivo. These data indicate that T/t-common can inhibit the ability of SK-OV-3 cancer cells to induce angiogenesis. T/t-common was found to be able to downregulate the expression of several proangiogenic factors, including vascular endothelial growth factor-A, interleukin-8, basic fibroblast growth factor, matrix metalloproteinase-2 and urokinase-type plasminogen activator, and upregulate antiangiogenic factors, including thrombospondin-1 and tissue inhibitor of metalloproteinases-1 in SK-OV-3 cancer cells. Finally, we demonstrated that T/t-common could inhibit the angiogenesis and growth of HER2-overexpressing human ovarian tumor in NOD/SCID mice. Taken together, the data suggest that T/t-common had the potential to be developed as a new antiangiogenic agent specific for treating HER2-overexpressing ovarian cancers.
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: S-P
authors.initials: SP
authors.lastname: Hsueh
authors.forename: W-B
authors.initials: WB
authors.lastname: Hsu
authors.forename: C-C
authors.initials: CC
authors.lastname: Wen
authors.forename: W-B
authors.initials: WB
authors.lastname: Wang
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000627:therapeutic use*; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D009389:Neovascularization, Pathologic / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000628:therapy*; D010455:Peptides / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000952:Antigens, Polyomavirus Transforming; D017077:Culture Media, Conditioned; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human