Loss of heterozygosity and p53 expression in Pterygium.

While the pathogenesis of pterygium is still not well understood, environmental factors such at UV light, appear to play an important role in its development. UV radiation can cause mutations in genes such as the p53 tumor suppressor gene, that when inactivated through mutation and loss of heterozygosity can lead to cell proliferation and genomic instability. However, aside from mutations in the gene, other mechanisms have been identified that can lead to loss of p53 function. These include the interaction of the p53 protein with cellular or viral gene products that lead to the inactivation of p53 or to its rapid degradation as well as the silencing of transcription of the p53 gene through the aberrant expression of factors that control p53 expression. We have analyzed the status and expression of the p53 gene in epithelial cells derived from pterygium and have demonstrated that the p53 gene has undergone a monoallelic deletion. Assays for both p53 protein and mRNA revealed that the remaining allele in these cells is not expressed at detectable levels. Furthermore, the remaining allele, by DNA sequence analysis appears to remain wild type. The mechanism of silencing the p53 gene and the loss of p53 expression in these cells is currently under investigation.

[1]  T. Reid,et al.  P53 expression in altered limbal basal cells of pingueculae, pterygia, and limbal tumors. , 1997, Current eye research.

[2]  I. Constable,et al.  Severe corneoscleral infection. A complication of beta irradiation scleral necrosis following pterygium excision. , 1993, Archives of ophthalmology.

[3]  A. Levine p53, the Cellular Gatekeeper for Growth and Division , 1997, Cell.

[4]  J. Simon,et al.  A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Xin Lu,et al.  Live or let die: the cell's response to p53 , 2002, Nature Reviews Cancer.

[6]  C. Onur,et al.  Expression of p53 Protein in Pterygium , 1998, European journal of ophthalmology.

[7]  Moshe Oren,et al.  Regulation of p53: intricate loops and delicate balances. , 2002, Biochemical pharmacology.

[8]  D. English,et al.  Sun exposure and pterygium of the eye: a dose-response curve. , 1999, American journal of ophthalmology.

[9]  S. Sukumar,et al.  Compromised HOXA5 function can limit p53 expression in human breast tumours , 2000, Nature.

[10]  V. Rotter,et al.  Oncogenic mutations of the p53 tumor suppressor: the demons of the guardian of the genome. , 2000, Cancer research.

[11]  D. Tan,et al.  Pterygium: prevalence, demography and risk factors. , 1999, Ophthalmic epidemiology.

[12]  A. Ziegler,et al.  Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancers. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[13]  A. Sarasin,et al.  The molecular pathways of ultraviolet-induced carcinogenesis. , 1999, Mutation research.

[14]  N. Hayward,et al.  Spontaneous and 4-nitroquinoline 1-oxide-induced G2 chromosome aberrations in lymphoblasts from familial melanoma patients. , 1989, Cancer genetics and cytogenetics.

[15]  K. Tsubota,et al.  Telomerase activity and p53 expression in pterygia. , 2000, Investigative ophthalmology & visual science.

[16]  W. Loging,et al.  Transcriptional regulation of the p53 tumor suppressor gene. , 1998, Seminars in cancer biology.

[17]  D. Albert,et al.  p53 expression and relation to human papillomavirus infection in pingueculae, pterygia, and limbal tumors. , 1999, Archives of ophthalmology.

[18]  G. Sourvinos,et al.  Microsatellite instability and loss of heterozygosity in human pterygia , 1997, The British journal of ophthalmology.