Retinoblastoma has properties of a cone precursor tumor and depends upon cone-specific MDM2 signaling Journal Article
| Authors: | Xu, X. L.; Fang, Y.; Lee, T. C.; Forrest, D.; Gregory-Evans, C.; Almeida, D.; Liu, A.; Jhanwar, S. C.; Abramson, D. H.; Cobrinik, D. |
| Article Title: | Retinoblastoma has properties of a cone precursor tumor and depends upon cone-specific MDM2 signaling |
| Abstract: | Retinoblastomas result from the inactivation of the RB1 gene and the loss of Rb protein, yet the cell type in which Rb suppresses retinoblastoma and the circuitry that underlies the need for Rb are undefined. Here, we show that retinoblastoma cells express markers of postmitotic cone precursors but not markers of other retinal cell types. We also demonstrate that human cone precursors prominently express MDM2 and N-Myc, that retinoblastoma cells require both of these proteins for proliferation and survival, and that MDM2 is needed to suppress ARF-induced apoptosis in cultured retinoblastoma cells. Interestingly, retinoblastoma cell MDM2 expression was regulated by the cone-specific RXRγ transcription factor and a human-specific RXRγ consensus binding site, and proliferation required RXRγ, as well as the cone-specific thyroid hormone receptor-β2. These findings provide support for a cone precursor origin of retinoblastoma and suggest that human cone-specific signaling circuitry sensitizes to the oncogenic effects of RB1 mutations. © 2009 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; controlled study; unclassified drug; gene mutation; nonhuman; cell proliferation; mouse; animals; mice; cell survival; apoptosis; signaling; animal experiment; animal model; retinoblastoma; carcinogenesis; gene expression regulation; stemcell; transplantation, heterologous; binding site; neoplasm transplantation; proto-oncogene proteins c-myc; retinoblastoma protein; oncogene c myb; humdisease; protein mdm2; proto-oncogene proteins c-mdm2; adenosine diphosphate ribosylation factor; retinoid x receptor gamma; thyroid hormone receptor beta; thyroid hormone receptor beta2; photoreceptor; retina cone; retinal cone photoreceptor cells; thyroid hormone receptors beta |
| Journal Title: | Cell |
| Volume: | 137 |
| Issue: | 6 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2009-01-01 |
| Start Page: | 1018 |
| End Page: | 1031 |
| Language: | English |
| DOI: | 10.1016/j.cell.2009.03.051 |
| PUBMED: | 19524506 |
| PROVIDER: | scopus |
| PMCID: | PMC5659855 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 19" - "Export Date: 30 November 2010" - "CODEN: CELLB" - "Source: Scopus" |
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