[Increased expression of the MYCN oncogene in human neuroblastoma cells and possible, new therapeutic approaches].
Human neuroblastomas of advanced stages often display amplification with a consecutive enhanced expression of the MYCN oncogene. Enhanced MYCN expression is thought to contribute in a causative manner to the progression of neuroblastomas, but the mechanisms by which this may occur have remained unclear. By transfecting human neuroblastoma cells that display a normal MYCN expression with the human MYCN oncogene, we have generated a cell line with enhanced MYCN expression and thereby were able to compare the biological and biochemical properties of the transfected and non-transfected cells. We have demonstrated autocrine growth factors in the MYCN-transfected, but not the non-transfected, neuroblastoma cells. Identification of the primary structures of these factors may help to develop specific antagonists in order to improve the therapy of advanced neuroblastomas. Currently, this could be done by application of genistein or tumor necrosis factor. As we could demonstrate for the first time, the dietary constituent genistein is able to inhibit the proliferation of neuroblastoma cells with enhanced and normal MYCN expression, but also that of cells derived from other solid pediatric tumors. In contrast, tumor necrosis factor is able to inhibit selectively the proliferation of neuroblastoma cells with enhanced MYCN expression. We suggest that tumor necrosis factor might improve the therapy of advanced human neuroblastomas.
Sektion Onkologie/Immunologie, Universitäts-Kinderklinik, Ruprecht-Karls-Universität Heidelberg.
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D000818:Animals; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002648:Child; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D014162:Transfection / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D016271:Proto-Oncogene Proteins c-myc; D014409:Tumor Necrosis Factor-alpha
Erhöhte Expression des MYCN Onkogens in humanen Neuroblastomzellen und mögliche, neue Therapie-Ansätze.