p53, proto-oncogene and rheumatoid arthritis

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Abstract

Objective: To review the literature published in the past 6 years concerning the role of p53 tumor-suppressor protein in rheumatoid arthritis (RA). Methods: A MEDLINE search was performed to identify all publications that covered the role of p53 in RA. In addition, selected articles related to proto-oncogenes and matrix metalloproteinases were included in this review. Results: p53 protein is expressed in RA fibroblast-like synoviocytes (FLSs), and its overexpression is a characteristic feature of RA. The overexpression of p53 is probably induced by DNA strand breaks caused by the genotoxic environment of RA joints, in some cases because of p53 mutations. Independent studies from 3 groups indicated that p53 mutations can and do occur in RA synovial tissue samples derived from a subset of RA patients. Inactivation of p53 may contribute to the invasiveness of FLSs and to the high-level expression of cartilage degradation enzymes as well. Gene transfer or gene knockout studies using a collagen-II-induced RA animal model to examine the role of p53 in RA have been reported. Initial results are positive and indicate that gene transfer of p53 may be clinically useful for the management of RA. Conclusions: p53 protein is expressed in RA FLSs, and its overexpression is a characteristic feature of RA. p53 mutations occur in the synovial tissues derived from a subset of RA patients. The clinical implications of p53 expression and the functional importance of somatic mutations in RA, however, are still unclear. Further research is needed to fully understand the implications of these findings and develop corresponding new therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)299-310
Number of pages12
JournalSeminars in Arthritis and Rheumatism
Volume31
Issue number5
DOIs
StatePublished - Jan 1 2002

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Keywords

  • Apoptosis
  • Gene therapy
  • Metalloproteinases
  • Proto-oncogenes
  • Rheumatoid arthritis
  • Synovium hyperplasia
  • Tumor suppressor protein p53

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Orthopedics and Sports Medicine
  • Rheumatology

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