The murine mammary epithelial cells HC11 were used as a model to examine cooperation between mutated p53 and activated oncogenes for cell growth and transformation. These cells lack wild-type (wt) p53 and their proliferation in monolayer is inhibited by reitroduction of wt p53. Expression of the ras, raf, erbB-2 and fgf-3 (former int-2) oncogenes in HC11 cells leads to their growth in soft-agar, a parameter of cell transformation. Clonogenicity in soft-agar of the ras, raf and erbB-2 transformed 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, transformed cells was retarded by ts p53 at 32 degrees C. Thus, ras, raf and fgf-3 oncogenes can partly or completely overcome the proliferation inhibitory function of wt p53, while erbB-2 cannot. These data indicate that specific oncogenes can distinctly cooperate with p53 for growth and transformation of mammary cells.

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