Altered expression of wild-type p53 tumor suppressor gene during murine epithelial cell transformation.
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.
Program of Biochemistry, Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York 14263.
K A
KA
Han
M F
MF
Kulesz-Martin
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002471:Cell Transformation, Neoplastic; D002999:Clone Cells; D004847:Epithelial Cells; D015870:Gene Expression; D016158:Genes, p53; D015151:Immunoblotting; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics
D009838:Oligodeoxyribonucleotides; D016159:Tumor Suppressor Protein p53; D012313:RNA