Abstract:
PURPOSE:To understand the genetic regulatory pathways underlying the retinoic acid (RA) induction of cone arrestin, gene array technology and other molecular tools were used to profile global gene expression changes in human retinoblastoma cells. METHODS:Weri-Rb-1 retinoblastoma cells were cultured in the absence or presence of RA for various periods. DNA microarray analysis profiled gene expression followed by real-time PCR and Northern and immunoblot analyses to confirm the change in expression of selected retinal genes and their gene products. Additional methodology included flow cytometry analysis, immunocytochemistry, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. RESULTS:DNA microarray analysis of approximately 6800 genes revealed RA-induced upregulation of cone-specific genes and downregulation of rod-specific genes in Weri-Rb-1 cells. Other significantly upregulated mRNAs included chicken ovalbumin upstream promoter-transcription factor (COUP-TF1), retinoid X receptor (RXR)-gamma, thyroid hormone receptor (TR)-beta2, and guanylyl cyclase-activating protein (GCAP)-1. Real-time PCR and/or Northern blot analysis confirmed the expression changes of a subset of genes including the upregulation of a pineal- and retina-specific transcription factor, CRX. RA treatment also led to G(0)/G(1) cell cycle arrest and increased both the intensity of human cone arrestin (hCAR)-immunoreactivity and the number of apoptotic cells. The cell-cycle-arrest stage correlated with the observed microarray results in which the RA treatment downregulated critical genes such as cyclins (cyclin E, cyclin D3) and cyclin-dependent kinases (CDK5, CDK10). CONCLUSIONS:These data suggest that RA induces a subpopulation of retinoblastoma cells to differentiate toward a cone cell lineage while selectively leading other cells into apoptosis.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Li A,Zhu X,Brown B,Craft CMdoi
10.1167/iovs.02-0434keywords:
subject
Has Abstractpub_date
2003-03-01 00:00:00pages
996-1007issue
3eissn
0146-0404issn
1552-5783journal_volume
44pub_type
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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abstract::Scanning electron microscopic (SEM) observations of the rabbit retinal pigment epithelium (RPE) are reported both for normal tissue and for tissue subjected to laser radiation. In normal RPE, cells were observed to be closely packed and to have the characteristic hexagonal shape. The microvilli were abundant and of tw...
journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1977-01-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1997-07-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2001-07-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1999-05-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 临床试验,杂志文章
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1987-05-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1983-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
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更新日期:2015-01-15 00:00:00
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更新日期:2009-06-01 00:00:00