Functional characterization of a heterozygous p53 innasopharyngeal carcinoma.

A74

The tumor suppressor function of p53 is compromised due to either gene mutation or alternative mechanisms in human cancer. We report here a functional characterization of a heterozygous p53 (p53^wt/280, one copy of wild type p53 and the other witha point mutation at codon 280) in an undifferentiated nasopharyngeal carcinoma (NPC) cell line CNE2. To elucidate the biological function of p53^wt/280, we employed the RNA interference (RNAi) approach to knockdown the endogenously expressed p53^wt/28 in CNE2 cells. Interestingly, suppression of p53^wt/280 expression in CNE2 cells was associated with significant down-regulation of p21^WAF1/CIP1 expression and decreased MDM2 protein level in both steady state and genotoxic stress induced by ionizing radiation. Consistent with these biochemical data were an accelerated cell cycle progression and an increased proliferation rate, suggesting that p53^wt/280 retained growth inhibitory activity in CNE2 cells. Indeed, down-regulation of p53^wt/280 in CNE2 enhanced the ability of CNE2 cells to grow anchorage-independently in vitro and to develop tumor in vivo. Together with the radio-resistance acquired by CNE2sip53 cells, our data indicate that p53^wt/280 in this NPC cell line remains functional, which may have an important therapeutical implication.