EFFECTS OF THE MYC ONCOGENE ANTAGONIST, MAD, ON PROLIFERATION, CELL CYCLING AND THE MALIGNANT PHENOTYPE OF HUMAN BRAIN-TUMOR CELLS

To investigate how overexpression of MAD, an antagonist of MYC oncogen es influences the malignant phenotype of human cancer cells, an adenov irus vector system was used to transfer the human MAD gene (AdMAD) int o human astrocytoma cells. Decreased growth potential of AdMAD-infecte d cells was evidenced by a decrease In [H-3]thymidine incorporation, a n increase in cell doubling time and alteration of cell-cycle distribu tion. Diminished malignant potential of AdMAD-infected cells was manif ested by their loss of anchorage-independent growth in soft agar and b y their inability, in general, to induce tumorigenesis in a xenograft animal model. These studies indicate that adenovirus constructs encodi ng MAD dramatically inhibit the proliferation and tumorigenicity of hu man astrocytoma cells and support the use of MAD for gene therapy of h uman tumours.