INDUCIBLE EXPRESSION OF MAD ACCELERATES GROWTH ARREST OF SERUM-DEPRIVED HUMAN GLIOBLASTOMA CELLS

Mad is a basic-helix-loop-helix leucine zipper protein that heterodimerizes with Max. Mad:Max heterodimers recognize the same DNA binding sites as Myc:Max heterodimers. However, Myc and Mad are thought to influence transcription and cell proliferation in opposite ways through interaction with Max. While Myc activates transcription and cell proliferation Mad represses these activities (Ayer et. al., Cell 72, 211-222, 1993). We have constructed an expression vector containing the mad cDNA cloned downstream of an inducible viral promoter. Cell lines carrying the construct were derived by transfection into human glioblastoma cells and the effect of Mad induction on their growth rate was studied. When the cells were cultured in low serum concentrations (0.1%) Mad induction resulted in accelerated growth arrest. These findings are consistent with the proposed growth repression function of the Mad protein.