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Cellular Adhesion Regulates p53 Protein Levels in Primary Human Keratinocytes¹

Department of Pathology, University of California, San Francisco, San Francisco, California 94143-0506 [J. M. N., K. D. A., T. D. T.]; and Department of Radiation Oncology, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina 27599-7512 [S. M. H.]

To gain insight into p53 tissue-specific regulatory pathways and biological activities, we investigated mechanisms that may account for the elevated levels of p53 protein in human foreskin keratinocytes, relative to levels in dermal fibroblasts in vitro. Here, we report that the loss of cell anchorage resulted in an approximately 5-fold decrease in p53 levels in keratinocytes, which was reversible upon reattachment of cells to a substratum. In contrast, fibroblasts did not exhibit such adhesion-dependent regulation of p53 protein. Furthermore, p53 function was attenuated in keratinocytes relative to fibroblasts. These results link p53 to cell adhesion pathways and may provide a molecular basis for epigenetic differences in the maintenance of genomic stability among normal cell types.

¹ This work was supported by NCI Grants CA 58207-04 and CA 51912-07 (T. D. T.); American Cancer Society Grant PF-4153 and The Environmental Pathology Training Grant 5T32 ES07106-15 (J. M. N.); Toxicology Training Grant 5T32 ES07126 (S. M. H.).

² To whom requests for reprints should be addressed. Phone: (415) 502-6115; Fax: (415) 502-6163; E-mail: ttlsty@itsa.ucsf.edu.

Received 6/11/97. Accepted 7/18/97.

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