title: High activin A-expression in human neuroblastoma: suppression of malignant potential and correlation with favourable clinical outcome.
abstract: Amplification of the MYCN oncogene contributes to the malignant progression of human neuroblastomas, but the mechanisms have remained unclear. We have previously demonstrated that N-Myc facilitates angiogenesis by downregulating an angiogenesis inhibitor identified as the inhibin betaA homodimer activin A. Here, we have sought to define the molecular, biological and clinical consequences of activin A expression in human neuroblastoma. We report that enhanced activin A expression suppresses proliferation and colony formation of human neuroblastoma cells with amplified MYCN in vitro; that it inhibits neuroblastoma growth and angiogenesis in vivo; that it is highly expressed in differentiated, but not undifferentiated human neuroblastomas; and that it correlates with favourable outcome of neuroblastoma patients. Our results indicate that high activin A expression plays an important beneficial role in human neuroblastoma.
authors.affiliation: Abteilung für Hämatologie, Onkologie und Endokrinologie, Universitäts-Kinderklinik Essen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schramm
authors.forename: Volker
authors.initials: V
authors.lastname: von Schuetz
authors.forename: Holger
authors.initials: H
authors.lastname: Christiansen
authors.forename: Werner
authors.initials: W
authors.lastname: Havers
authors.forename: Maria
authors.initials: M
authors.lastname: Papoutsi
authors.forename: Jörg
authors.initials: J
authors.lastname: Wilting
authors.forename: Lothar
authors.initials: L
authors.lastname: Schweigerer
mesh_terms: D028341:Activins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D028322:Inhibin-beta Subunits / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: C422405:activin A; D028341:Activins; D028322:Inhibin-beta Subunits