Abstract
An epidermal cell model in which initiated, benign tumor-producing and carcinoma stages were derived from a cloned parental cell strain was used to examine p53 expression during multistage epithelial carcinogenesis. Increased steady-state levels of p53 RNA were detected in squamous cell carcinomas compared to papilloma and normal epidermal cells. Nontumorigenic initiated cell precursors of the carcinomas exhibited normal p53 expression, localizing altered p53 regulation to the malignant conversion stage. Immunoprecipitation and Western immunoblot analyses demonstrated elevated levels of p53 protein in the moderately differentiated carcinoma compared to normal cells, and negligible levels of p53 in the poorly differentiated carcinoma cells. Sequence analysis of p53 complementary DNA from normal and carcinoma cells revealed no mutations in the coding or 5′- and 3′-untranslated regions, suggesting a novel mechanism of p53 inactivation.
Footnotes
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↵1 This work was supported by NIH Grants CA31101, CA13038, Biomedical Research Support Grant S07 RR05648, and CA16056.
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↵2 To whom requests for reprints should be addressed.
- Received November 7, 1991.
- Accepted December 10, 1991.
- ©1992 American Association for Cancer Research.
Volume 52, Issue 3
