The RET oncogene is a critical component of transcriptional programs associated with retinoic acid-induced differentiation in neuroblastoma Journal Article
| Authors: | Oppenheimer, O.; Cheung, N. K.; Gerald, W. L. |
| Article Title: | The RET oncogene is a critical component of transcriptional programs associated with retinoic acid-induced differentiation in neuroblastoma |
| Abstract: | Differentiation is a key feature in pathologic classification and prognosis of neuroblastic tumors, although the underlying molecular mechanisms are not well defined. To identify key differentiation-related molecules and pathways, we evaluated gene expression during retinoic acid (RA) - induced differentiation of seven neuroblastic tumor cell lines. Transcriptional response to RA was highly variable among cell lines despite the fact that six of seven showed similar morphologic changes. RA consistently altered expression of a small set of genes, some of which are known to play a role in neurogenesis and differentiation. Expression of genes that were regulated by RA was associated with important clinical subgroups of neuroblastic tumors and were differentially expressed by stroma-rich and stroma-poor subtypes. RET, a receptor tyrosine kinase involved with differentiation, was consistently up-regulated throughout the time course of RA treatment in the majority of neuroblastic tumor cell lines. Interference with RET activation abrogated RA-induced transcriptional programs and differentiation, suggesting a key role of RET in this process. The core set of RA-regulated genes includes critical molecular components of pathways necessary for neuroblastic tumor differentiation and have potential as therapeutic targets and molecular markers of response to differentiating agents. Copyright © 2007 American Association for Cancer Research. |
| Keywords: | controlled study; human tissue; human cell; major clinical study; drug targeting; cell structure; proto oncogene; cluster analysis; gene expression profiling; tumor differentiation; small interfering rna; rna, small interfering; cell differentiation; transcription, genetic; cancer cell culture; enzyme activation; cell line, tumor; protein tyrosine kinase; phosphorylation; time; molecular marker; gene expression regulation; gene expression regulation, neoplastic; transcription regulation; neuroblastoma; rna, messenger; vandetanib; upregulation; stroma cell; nervous system development; protein ret; retinoic acid; proto-oncogene proteins c-ret; genes, neoplasm; tretinoin |
| Journal Title: | Molecular Cancer Therapeutics |
| Volume: | 6 |
| Issue: | 4 |
| ISSN: | 1535-7163 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2007-04-01 |
| Start Page: | 1300 |
| End Page: | 1309 |
| Language: | English |
| DOI: | 10.1158/1535-7163.mct-06-0587 |
| PUBMED: | 17431108 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 12" - "Export Date: 17 November 2011" - "CODEN: MCTOC" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work