COOPERATION BETWEEN MUTANT P53 AND THE RAS, RAF, ERBB-2 AND FGF-3 ONCOGENES FOR TRANSFORMATION OF MAMMARY EPITHELIAL-CELLS

The murine mammary epithelial cells HC11 were used as a model to exami ne cooperation between mutated p53 and activated oncogenes for cell gr owth and transformation. These cells lack wild-type (wt) p53 and their proliferation in monolayer is inhibited by reitroduction of wt p53. E xpression of the ras, raf, erbB-2 and fgf-3 (former int-2) oncogenes i n HC11 cells leads to their growth in soft-agar, a parameter of cell t ransformation. Clonogenicity in soft-agar of the ras, raf and erbB-2 t ransformed cells was inhibited by a temperature-sensitive (ts) p53 at 32 degrees C, when the ts p53 protein is wt. Thus these oncogenes act synergistically with mutant p53 to induce anchorage-independent growth . Proliferation in monolayer of erbB-2, but not ras, raf, or fgf-3, tr ansformed cells was retarded by ts p53 at 32 degrees C. Thus, ras, raf and fgf-3 oncogenes can partly or completely overcome the proliferati on inhibitory function of wt p53, while erbB-2 cannot. These data indi cate that specific oncogenes can distinctly cooperate with p53 for gro wth and transformation of mammary cells.