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. Our data provide direct evidence for the tumor-suppressive activity of p21WAF1.

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Supported in part by American Cancer Society Grant IN-162 and a fund from the Pathology Department, Wayne State University.

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