Altered structure and expression of RB1 gene and increased phosphorylation of pRb in human vestibular schwannomas

R. Thomas, P. D.Antony Herold Prabhu, J. Mathivanan, Rohini, D. Sivakumar, P. N. Jayakumar, B. Indira Devi, S. Satish, K. V.R. Sastry, R. Gope

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Abstract

Tumor-specific alterations at the RB1 gene locus in 30 human vestibular schwannomas including 10 NF2 and 20 sporadic cases were analysed. Southern blot analysis of DNA from these samples revealed loss of heterozygosity (LOH) at the RB1 locus in 6 of 24 informative cases (25%) compared to normal blood DNAs from the same patients. Northern blot analysis showed normal size RB1 mRNA in all the tumor samples. However, there was a 2-5-fold increase in the level of expression of the RB1 gene in all the tumor samples compared to the WI38 cell line which was used as control. Western blot analysis of the RB1 protein, pRb showed a 2.5-5-fold increase in the level of total pRb as compared to normal WI38 cell line. Sixty five to seventy five percent of the total pRb were in phosphorylated form in most tumors. The LOH at the RB1 gene locus suggests genetic instability in these patients. Further, increased levels of RB1 mRNA, total pRb and the phosphorylated form of pRb suggests that RB1gene in these tumors may have anti-apoptotic function. These results suggest that the RB1 gene has a major role in the development of human vestibular schwannomas.

Original languageEnglish
Pages (from-to)113-121
Number of pages9
JournalMolecular and Cellular Biochemistry
Volume271
Issue number1-2
DOIs
Publication statusPublished - 1 Mar 2005

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Keywords

  • Gene expression
  • Gene structure
  • Human retinoblastoma gene (RB1)
  • Human vestibular schwannomas
  • Tumor suppressor gene
  • pRb
  • pRb phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Thomas, R., Prabhu, P. D. A. H., Mathivanan, J., Rohini, Sivakumar, D., Jayakumar, P. N., Devi, B. I., Satish, S., Sastry, K. V. R., & Gope, R. (2005). Altered structure and expression of RB1 gene and increased phosphorylation of pRb in human vestibular schwannomas. Molecular and Cellular Biochemistry, 271(1-2), 113-121. https://doi.org/10.1007/s11010-005-5617-0