Altered growth response of oral mucosal keratinocytes in p53-deficient mice

P53 has important regulatory functions in cell growth, differentiation and apoptosis. Here we analyzed the effects of p53 on the growth response of or al mucosal keratinocytes (OMKCs) using p53-deficient (p53-/-) mice. No morp hological difference was found between p53-/- and wild-type (p53+/+) oral m ucosa. In a long-term culture, p53-/- OMKCs continued to proliferate past t he point at which p53 +/+ became senescent. The percentage of p53 -/- OMKCs in the G(0)/G(1) phase was lower than that of p53 +/+ OMKCs. Proliferation of cultured OMKCs induced by epidermal growth factor (EGF) and interleukin (IL)-1 alpha was more strongly enhanced in p53-/- than in p53+/+ mice. Such an enhanced response was not due to increased mRNA expression of growth fa ctor receptors. These data suggest that p53 acts as a modulator of GI arres t in OMKCs and is also involved in the regulation of responses to EGF and I L-1 alpha without affecting the expression of their receptors.