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Genetic and epigenetic alterations of RB2/p130 tumor suppressor gene in human sporadic retinoblastoma: implications for pathogenesis and therapeutic approach.
- Source :
-
Oncogene [Oncogene] 2005 Sep 01; Vol. 24 (38), pp. 5827-36. - Publication Year :
- 2005
-
Abstract
- Human retinoblastoma occurs in two forms (familial and sporadic) both due to biallelic mutation of the RB1/p105 gene even if its loss is insufficient for malignancy. We have recently reported that loss of expression of the retinoblastoma-related protein pRb2/p130 correlates with low apoptotic index, suggesting that RB2/p130 gene could be involved in retinoblastoma. Mutational analysis of RB2/p130 in primary tumors showed a tight correlation between Exon 1 mutations and pRb2/p130 expression level in sporadic retinoblastoma. These mutations are located within a CpG-enriched region prone to de novo methylation. Analysis of RB2/p130 methylation status revealed that epigenetic events, most probably consequent to the Exon 1 mutations, determined the observed phenotype. Treatment of Weri-Rb1 cell line by 5-Aza-dC induced an increase in expression level of pRb2/p130, E2F1, p73 and p53. Overall, our results highlight a crucial role of epigenetic events in sporadic retinoblastoma, which opens a perspective for new therapeutic approaches.
- Subjects :
- Azacitidine analogs & derivatives
Azacitidine pharmacology
Base Sequence
Blotting, Western
Cell Line, Tumor
Cell Proliferation drug effects
DNA Methylation drug effects
DNA Mutational Analysis
DNA Primers
Decitabine
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Molecular Sequence Data
Retinoblastoma-Like Protein p130
Epigenesis, Genetic
Genes, Tumor Suppressor
Proteins genetics
Retinal Neoplasms genetics
Retinoblastoma genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0950-9232
- Volume :
- 24
- Issue :
- 38
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 16007224
- Full Text :
- https://doi.org/10.1038/sj.onc.1208630