The p53R2 gene encodes the
ribonucleotide reductase (RR) small subunit 2 homologue, and is induced by several stress signals activating p53, such as
DNA-damaging agents. The p53R2 gene product causes an increase in the deoxynucleotide
triphosphate (dNTP) pool in the nucleus, which facilitates DNA repair and synthesis. We hypothesized that p53R2 would be a good molecular target for cancer gene
therapy. In this study, three human
oral cancer cell lines (SAS, HSC-4 and Ca9-22), a human
breast cancer cell line MCF-7, and a normal human fibroblast cell line NHDF were tested. We silenced the expression of p53R2 with the highly specific post-transcriptional suppression of RNA interference (RNAi). We investigated p53R2 expression with the reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The sensitivity to
anticancer agents was evaluated by a
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of p53R2 showed no association with the mutational status of p53. The
cancer cell lines with higher p53R2 expression were more resistant to
5-FU. RNAi-mediated p53R2 reduction selectivity inhibited growth and enhanced chemosensitivity in
cancer cell lines but not in normal fibroblasts. These results suggest that basal transcription of p53R2 could be associated with the sensitivity to
anticancer agents. Moreover, we assessed the possibility that p53R2 would be a good molecular target, and report that RNAi targeting of p53R2 could be useful for
oral cancer gene therapy.