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 oral mucosal keratinocytes (OMKCs) using p53-deficient (p53-/-) mice. No morphological difference was found between p53-/- and wild-type (p53+/+) oral mucosa. In a long-term culture, p53-/- OMKCs continued to proliferate past the point at which p53+/+ became senescent. The percentage of p53-/- OMKCs in the G0/G1 phase was lower than that of p53+/+ OMKCs. Proliferation of cultured OMKCs induced by epidermal growth factor (EGF) and interleukin-(IL)-1alpha was more strongly enhanced in p53-/- than in p53+/+ mice. Such an enhanced response was not due to increased mRNA expression of growth factor receptors. These data suggest that p53 acts as a modulator of G1 arrest in OMKCs and is also involved in the regulation of responses to EGF and IL-1alpha without affecting the expression of their receptors.
Ito
D
D
Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Tokyo, Japan.
Kamijo
R
R
Nakanishi
Y
Y
Toyoshima
T
T
Takizawa
K
K
Sumitani
K
K
Nagumo
M
M
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009061:Mouth Mucosa / Q000002:abnormalities / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D016159:Tumor Suppressor Protein p53; D004815:Epidermal Growth Factor; D066246:ErbB Receptors