Genetic and epigenetic alterations of RB2/p130 tumor suppressor gene in human sporadic retinoblastoma: Implications for pathogenesis and therapeutic approach

Aldo Caporossi, Gian Marco Tosi, Carmela Trimarchi, Marcella Macaluso, Dario La Sala, Alfredo Ciccodicola, Stefano Lazzi, Mina Massaro-Giordano, Antonio Giordano, Caterina Cinti

Research output: Contribution to journalArticle

28 Citations (Scopus)

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. © 2005 Nature Publishing Group. All rights reserved.
Original languageEnglish
Pages (from-to)5827-5836
Number of pages10
JournalOncogene
Volume24
DOIs
Publication statusPublished - 2005

Keywords

  • 5-Aza-dC
  • Azacitidine
  • Base Sequence
  • Blotting, Western
  • Cancer Research
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA Methylation
  • DNA Mutational Analysis
  • DNA Primers
  • Demethylating agent
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Genetics
  • Humans
  • Immunohistochemistry
  • Methylation
  • Molecular Biology
  • Molecular Sequence Data
  • Proteins
  • Rb2/p130 mutation
  • Retinal Neoplasms
  • Retinoblastoma
  • Retinoblastoma-Like Protein p130
  • Sporadic retinoblastoma

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