High activin A-expression in human neuroblastoma: suppression of malignant potential and correlation with favourable clinical outcome.
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.
Schramm
Alexander
A
Abteilung für Hämatologie, Onkologie und Endokrinologie, Universitäts-Kinderklinik Essen, Germany.
von Schuetz
Volker
V
Christiansen
Holger
H
Havers
Werner
W
Papoutsi
Maria
M
Wilting
Jörg
J
Schweigerer
Lothar
L
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
C422405:activin A; D028341:Activins; D028322:Inhibin-beta Subunits