Tumor suppression by p21WAF1.

The p21WAF1 gene encodes a cyclin-dependent kinase inhibitor and mediates tumor suppressor gene p53-induced cell cycle arrest. To directly test whether p21WAF1 can act as a tumor suppressor, we have expressed the p21WAF1 cDNA in several human tumor cell lines using a tetracycline-inducible system. Overexpression of p21WAF1 suppresses proliferation and soft agar growth of tumor cells in vitro, as well as tumorigenicity in vivo.

P53-independent induction of p21(waf1) pathway is preserved during tumor progression.

The p21(WAF1) gene encodes a cyclin-dependent kinase inhibitor and plays an important role in controlling the cell cycle. Its expression can be induced through wild-type p53-dependent or -independent pathways. Since the p53-dependent pathway is disrupted in more than 50% of human tumors, we wondered whether the p53-independent pathway is also altered during tumor progression.