Protein levels of NAD(P)H:quinone oxidoreductase 1 and p53 correlate in breast tumors.

Abstract

Abstract Abstract #4157 Background: NAD(P)H:quinone oxidoreductase 1 (NQO1) is integral flavoprotein responsible for detoxification and metabolism of quinoid compounds. NQO1 protects cells against accumulation of genotoxic quinoids, oxidative stress and stabilizes p53 from proteasomal degradation. The aim of this study was to follow the NQO1 role in breast carcinogenesis.
 Methods: Levels of NQO1 transcript were monitored in frozen tumor samples by real-time PCR with absolute quantification. NQO1 protein levels were evaluated by immunohistochemistry in paraffin-embedded tumor samples. NQO1-Pro187Ser polymorphism was assessed in lymphocyte DNA by PCR with restriction fragment analysis.
 Results: High interindividual variability in NQO1 expression among patients was observed. Wild-type genotype samples expressed NQO1 protein more often than heterozygotes (p=0.004; Fisher's exact test). We found strong correlation between NQO1 transcript and protein levels (p=0.004; T-test). Moreover, samples with negative NQO1 protein expression were often also negative for p53 expression (p=0.037; Fisher's exact test). No significant association of NQO1 levels and/or polymorphism with clinico-pathological characteristics of patients was found.
 Conclusions: One of major findings of this study is the observed correlation of protein levels of NQO1 and p53 in breast tumors. Ability of NQO1 to modulate the degradation of p53 in the 20S proteasome was previously reported by use of cell lines and animal models [1]. Our results obtained by the use of real tumor samples further support this concept and suggest that NQO1 may play important role in carcinogenesis.
 This study was supported by grants of Internal Grant Agency of Ministry of Health of the Czech Republic, no.: 9426-3, Grant Agency of the Czech Republic 305/07/P347 and the Grant Agency of Charles University, no.: 94507.1. Asher G, Lotem J, Kama R, Sachs L, Shaul Y: Proc Natl Acad Sci USA 98(3): 1188-1193, 2001. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4157.