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The p16 gene, encodes a key checkpoint protein p16 in the cell cycle, has been reported inactivation in a wide variety of human cancers. We have previously demonstrated high frequency ofp16 alterations in primary nasopharyngeal carcinoma (NPC), xenografts and cell lines. The finding implied that inactivation of thep16 gene may play an important role in the NPC development. To investigate the tumour suppressor function ofp16 in NPC, we tranfectedp16-deficient NPC cell line, NPC/HK-1, with a wild-typep16 expression construct, and evaluated growth and tumorigenic properties of the clones stably expressing exogenous p16. Expression of the exogenous wild-typep16 significantly inhibited cell growth by more than 70% when compared to that of the parental and empty vector-transfected cells. This growth inhibition was attributable to a significant proportion of p16-expressing cells arrested at G1 phase in the cell cycle as revealed by flow cytometric analysis. By anchorage-independent colony forming assay, we found that the ability to form colonies in soft agar was highly reduced in cells expressing p16. NPC/HK1 cells expressing functional p16 also showed suppressed tumorigenicity in athymic nude mice. Taken together, our results provide strong evidence for a tumour suppressor role ofp16 in NPC. [ABSTRACT FROM AUTHOR]