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Allele-specific mRNA and protein expression on genetic variants of CCNE1 associated with risk of bladder cancer

Thursday, October 11, 2012 — Poster Session III

10:00 a.m. – Noon

Natcher Conference Center, Building 45



* FARE Award Winner


  • I. Kohaar
  • Y.P. Fu
  • W. Tang
  • M. Tarway
  • B. Muchmore
  • P. Porter-Gill
  • L. Prokunina-Olsson


A single nucleotide polymorphism (SNP), rs8102137, located 6 Kb upstream from the cyclin E1 gene (CCNE1) on chromosome 19q12, has recently been identified as a risk factor for bladder cancer (OR, p=1.7x10-11). We found a higher expression of CCNE1 mRNA in cDNA samples from bladder tumors (n=42) compared to adjacent normal bladder tissue (n=41, 3.7 fold, p=2.7x10-12). However, the expression did not correlate with genotypes of rs8102137. Western blot protein analysis with bladder tissue and cell lines lysates showed that this allele-specific difference in mRNA expression is likely to be related to two protein isoforms that showed a differential pattern of expression dependent on rs8102137 genotypes. CCNE1 regulates cell cycle G1/S transition, and alternative protein forms may have differential functions in cell cycle regulation, thereby affecting the risk of cancer. Alternative splicing forms of CCNE1 (with exon 7 and 9 deletion) in addition to the wild type have been cloned and their functional analysis is ongoing. In conclusion, our results suggest that bladder cancer associated genetic variants within the CCNE1 gene may affect mRNA splicing and protein structure of the gene, contributing to altered regulation of cell cycle and risk of bladder and other cancers.

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