ROLE OF THE P53 TUMOR-SUPPRESSOR GENE IN THE TUMORIGENICITY OF BURKITTS-LYMPHOMA CELLS

Burkitt's lymphoma (BL) cell lines carry a translocated c-myc gene and , in 60-80% of cases, exhibit mutations in the p53 tumor suppressor ge ne. We examined the potential role of the p53 gene in BL tumorigenicit y using an in vitro assay that measures p53-dependent cell cycle arres t in the G(1) phase of the cell cycle and an in vivo athymic murine mo del that detects differences in the tumorigenicity of BL cell lines. A highly significant inverse correlation was found between the ability of BL cells to arrest in G(1) after irradiation and their tumorigenici ty in athymic mice, consistent with the notion that loss of p53 functi on is associated with increased tumorigenicity. Inactivation of wild-t ype (wt) p53 function by expression of the human papillomavirus E6 pro tein in the AG876V BL cell line, which carries both wt and mutant p53 proteins, rendered the cell line significantly more tumorigenic in ath ymic mice. Transfection of the wt p53 gene into the p53 mutant and hig hly tumorigenic BL-41 cell line caused it to acquire wt p53 function a nd rendered it less tumorigenic in mice. In addition to confirming a r ole for the loss of p53 function in tumor progression, the data demons trate that wt p53 protein can reduce BL tumorigenicity in vivo.