Temporally regulated neural crest transcription factors distinguish neuroectodermal tumors of varying malignancy and differentiation Journal Article
| Authors: | Gershon, T. R.; Oppenheimer, O.; Chin, S. S.; Gerald, W. L. |
| Article Title: | Temporally regulated neural crest transcription factors distinguish neuroectodermal tumors of varying malignancy and differentiation |
| Abstract: | Neuroectodermal tumor cells, like neural crest (NC) cells, are pluripotent, proliferative, and migratory. We tested the hypothesis that genetic programs essential to NC development are activated in neuroectodermal tumors. We examined the expression of transcription factors PAX3, PAX7, AP-2α, and SOX10 in human embryos and neuroectodermal tumors: neurofibroma, schwannoma, neuroblastoma, malignant nerve sheath tumor, melanoma, medulloblastoma, supratentorial primitive neuroectodermal tumor, and Ewing's sarcoma. We also examined the expression of P0, ERBB3, and STX, targets of SOX10, AP-2α, and PAX3, respectively. PAX3, AP-2α, and SOX10 were expressed sequentially in human NC development, whereas PAX7 was restricted to mesoderm. Tumors expressed PAX3, AP-2α, SOX10, and PAX7 in specific combinations. SOX10 and AP-2α were expressed in relatively differentiated neoplasms. The early NC marker, PAX3, and its homologue, PAX7, were detected in poorly differentiated tumors and tumors with malignant potential. Expression of NC transcription factors and target genes correlated. Transcription factors essential to NC development are thus present in neuroectodermal tumors. Correlation of specific NC transcription factors with phenotype, and with expression of specific downstream genes, provides evidence that these transcription factors actively influence gene expression and tumor behavior. These findings suggest that PAX3, PAX7, AP-2α, and SOX10 are potential markers of prognosis and targets for therapeutic intervention. Copyright © 2005 Neoplasia Press, Inc. All rights reserved. |
| Keywords: | immunohistochemistry; human tissue; protein expression; unclassified drug; human cell; dna-binding proteins; phenotype; melanoma; gene expression; melanocyte; tumor markers, biological; transcription factor; cell differentiation; transcription, genetic; time factors; cell lineage; transcription factors; ewing sarcoma; gene expression regulation, developmental; gene expression regulation, neoplastic; neuroblastoma; rna, messenger; oligonucleotide array sequence analysis; medulloblastoma; development; neural crest; transcription factor pax3; sequence homology; epidermal growth factor receptor 3; nerve sheath tumor; mesoderm; neuroectoderm tumor; neurofibroma; paired box transcription factors; neurilemoma; glia; schwann cells; transcription factor pax7; neural crest cell; transcription factor ap 2; high mobility group proteins; neuroectodermal tumor; transcription factor p0; transcription factor sox10; transcription factor stx |
| Journal Title: | NeoPlasia |
| Volume: | 7 |
| Issue: | 6 |
| ISSN: | 1522-8002 |
| Publisher: | Elsevier Science Inc. |
| Date Published: | 2005-06-01 |
| Start Page: | 575 |
| End Page: | 584 |
| Language: | English |
| DOI: | 10.1593/neo.04637 |
| PUBMED: | 16036108 |
| PROVIDER: | scopus |
| PMCID: | PMC1501286 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 31" - "Export Date: 24 October 2012" - "CODEN: NEOPF" - "Source: Scopus" |
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