Down-regulation of endothelial cell growth inhibitors by enhanced MYCN oncogene expression in human neuroblastoma cells

Autor: Theodore Fotsis, Werner Lutz, Elissavet Hatzi, Stephen Breit, Lothar Schweigerer, Manfred Schwab, Jochen Rössler
Rok vydání: 1999
Předmět:
Cell Division/drug effects
Angiogenesis
Gene Expression Regulation
Neoplastic
Genes
myc
Biology
Biochemistry
Chromatography
Affinity
Malignant transformation
Proto-Oncogene Proteins c-myc
Neovascularization
Neuroblastoma
Downregulation and upregulation
Tumor Cells
Cultured
medicine
Humans
Recombinant Proteins/pharmacology
neoplasms
Cells
Cultured
Endothelium
Vascular/cytology/drug effects/*physiology
Neovascularization
Pathologic
Oncogene
Proto-Oncogene Proteins c-myc/*genetics
medicine.disease
Molecular biology
Growth Inhibitors
Recombinant Proteins
Endothelial stem cell
Cell Transformation
Neoplastic
Culture Media
Conditioned
Cancer research
Fibroblast Growth Factor 2/*pharmacology
Fibroblast Growth Factor 2
Growth Inhibitors/*biosynthesis/isolation & purification
Endothelium
Vascular
medicine.symptom
Cell Division
Endothelial cell growth
Zdroj: European Journal of Biochemistry. 263:757-764
ISSN: 1432-1033
0014-2956
DOI: 10.1046/j.1432-1327.1999.00575.x
Popis: Recent evidence indicates that the genetic alterations of the multistage process of malignant transformation appear to activate tumor neovascularization by altering the balance between stimulators and inhibitors of angiogenesis. In the present study, we have attempted to define the effect of enhanced MYCN oncogene expression on the profile of endothelial cell growth modulators in neuroblastoma cells. We report here that conditioned medium of human neuroblastoma cells with normal MYCN expression contains three inhibitors of endothelial cell proliferation, which appear to be novel proteins as judged by their physicochemical, immunological and biological properties. All three inhibitors are diminished or become undetectable upon experimental increase of MYCN expression. Our results suggest that enhanced MYCN expression in human neuroblastoma cells alters the angiogenic balance by down-regulating endothelial cell growth inhibitors but leaving the expression of the stimulators unaffected. These data shed light on the molecular mechanisms linking the genetic changes of malignant transformation with initiation of tumor angiogenesis. Moreover, our observations might explain the poor prognosis of human neuroblastomas following MYCN oncogene amplification through initiation of angiogenesis and subsequent tumor growth and spread. Eur J Biochem
Databáze: OpenAIRE
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