Age dependent phosphorylation and deregulation of p53 in human vestibular schwannomas

Antony H.P.P. Dayalan, Mathivanan Jothi, Rohini Keshava, Remy Thomas, Mohan L. Gope, Subbakrishna K. Doddaballapur, Sampath Somanna, Shanti S. Prabaraj, Chandramouli B. Ashwathnarayanarao, Rajalakshmi Gope

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Abstract

Tumor-specific alterations at the p53 gene locus in 30 human vestibular schwannomas (VS) comprising 10 confirmed NF2 cases and 20 sporadic cases were analyzed. We found loss of heterozygosity (LOH) at the first intron of the p53 gene locus in 54% of the informative cases. This is the first report showing LOH at the p53 gene locus in a significant number of human VS and both sporadic and NF2 cases show the LOH event. Increased levels of normal size p53 mRNA and p53 protein were found in all the tumors analyzed. Thus p53 appears to be deregulated in all the tumors suggesting that p53 alterations may be associated with tumor progression in VS. There was a negative significant correlation of patients' age and percentage of Ser 392 phosphorylated p53 protein. The tumor samples obtained from younger patients of 35 yr and below showed higher percentage of Ser 392 phosphorylated p53 protein compared to the tumors of older patients. The increased percentage of Ser 392 phosphorylated p53 protein indicates that it could be involved in the acceleration of tumor growth in the younger patients. Our results suggest that age dependent phosphorylation of p53 protein and deregulation of p53 gene has a role in the development of human vestibular schwannomas.

Original languageEnglish
Pages (from-to)38-46
Number of pages9
JournalMolecular Carcinogenesis
Volume45
Issue number1
DOIs
Publication statusPublished - 1 Jan 2006

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Keywords

  • Human vestibular schwannomas
  • LOH
  • Ser 392 phosphorylation
  • p53 mrna
  • p53 protein

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Dayalan, A. H. P. P., Jothi, M., Keshava, R., Thomas, R., Gope, M. L., Doddaballapur, S. K., Somanna, S., Prabaraj, S. S., Ashwathnarayanarao, C. B., & Gope, R. (2006). Age dependent phosphorylation and deregulation of p53 in human vestibular schwannomas. Molecular Carcinogenesis, 45(1), 38-46. https://doi.org/10.1002/mc.20150