title: The role of the MEIS homeobox genes in neuroblastoma.
abstract: We recently found amplification of the TALE homeobox gene MEIS1 in the IMR32 neuroblastoma cell line. We now demonstrate high-level expression of the MEIS1 and MEIS2 genes, as well as efficient expression of most other TALE family member genes in a panel of neuroblastoma cell lines. Stable transfection of MEIS1-expressing cell lines with cDNA encoding a naturally occurring dominant-negative splice variant of MEIS1 (MEIS1E) yielded clones with impaired cell proliferation, gain of differentiated phenotype, and increased contact inhibition and cell death. This indicated a relevance of MEIS expression for neuroblastoma cell growth and proliferation. We therefore determined the gene expression profiles of several MEIS1E transfectants using serial analysis of gene expression (SAGE). A large number of genes showed differential expression as a result of MEIS1E expression. These include genes involved in developmental signalling pathways, chromatin binding, cell cycle control, proliferation, and apoptosis. The results presented provide important clues for the oncogenic function of MEIS1 in neuroblastoma.
authors.affiliation: Department of Human Genetics M1-159, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. d.geerts@amc.uva.nl
authors.forename: Dirk
authors.initials: D
authors.lastname: Geerts
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schilderink
authors.forename: Gerda
authors.initials: G
authors.lastname: Jorritsma
authors.forename: Rogier
authors.initials: R
authors.lastname: Versteeg
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009857:Oncogenes / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins