Document Detail


Retinoblastoma has properties of a cone precursor tumor and depends upon cone-specific MDM2 signaling.
MedLine Citation:
PMID:  19524506     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 RXRgamma transcription factor and a human-specific RXRgamma consensus binding site, and proliferation required RXRgamma, as well as the cone-specific thyroid hormone receptor-beta2. 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.
Authors:
Xiaoliang L Xu; Yuqiang Fang; Thomas C Lee; Douglas Forrest; Cheryl Gregory-Evans; Dena Almeida; Aihong Liu; Suresh C Jhanwar; David H Abramson; David Cobrinik
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell     Volume:  137     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-15     Completed Date:  2009-07-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1018-31     Citation Subset:  IM    
Affiliation:
Dyson Vision Research Institute, Weill Cornell Medical College, New York, NY 10021, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Proliferation*
Cell Survival
Humans
Mice
Neoplasm Transplantation
Proto-Oncogene Proteins c-mdm2 / metabolism*
Proto-Oncogene Proteins c-myc / metabolism
Retinal Cone Photoreceptor Cells / metabolism
Retinoblastoma / metabolism*
Retinoid X Receptor gamma / metabolism
Signal Transduction*
Thyroid Hormone Receptors beta / metabolism
Transplantation, Heterologous
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-myc; 0/Retinoid X Receptor gamma; 0/Thyroid Hormone Receptors beta; EC 6.3.2.19/MDM2 protein, human; EC 6.3.2.19/Proto-Oncogene Proteins c-mdm2
Comments/Corrections
Comment In:
Cell. 2009 Jun 12;137(6):992-4   [PMID:  19524501 ]

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