The protein p53 is highly expressed in a large variety of transformed cell types originating from diverse species. These include cells transformed by Simian virus 40 (SV40), adenovirus and Abelson virus, as well as a variety of chemically transformed cells. Substantial amounts of p53 are also present in certain non-transformed cells, for example, some embryonic tissues. The protein may be localized in different cellular compartments in normal and transformed cells. The strong correlation between tumorigenicity and high levels of p53 suggests an important role of p53 in tumorigenesis. We report here experiments in which we have co-transfected the murine cellular gene encoding for p53 with a ras gene into primary rat embryo fibroblasts. Our results indicate that the p53-encoding gene can play a causal role in the conversion of normal fibroblasts into tumorigenic cells.
The tumor antigen p53 is overproduced in transformed cells of various species, including man. HL-60 is an exceptional human tumor cell line that does not express this protein. Hybridization of polyadenylylated mRNA of these cells with a human p53 cDNA probe (p53-H14), which we cloned, had indicated a total absence of the mature-size (3.0 kilobases) or any aberrant p53 mRNA species. Analysis of the genomic HL-60 DNA indicated that the p53 gene in these cells was significantly altered. Most of the gene was deleted, and the residual p53 sequences of these cells, which show weak homology, mapped to the corresponding 5' region of the p53 gene. In agreement with previously documented results, we found that HL-60 cells have an amplified c-myc gene. We suggest that the deficiency of the p53 protein in HL-60 cells could have been overcome by using an alternative metabolic pathway. The cmyc product is a candidate for such an alternative protein.The cell-encoded tumor antigen p53 is found at elevated levels in tumor cells of different tissue types and species (1-5). Similar-sized proteins were detected in mouse, rat, hamster, and human cells (2,(6)(7)(8) (Amersham, England). Cells were incubated for 1-5 hr at 37°C, washed in phosphate-buffered saline, and extracted into 2 ml of lysis buffer (10 mM Na2H-P04/NaH2PO4, pH 7.5/100 mM NaCl/1% Triton X-100/0.5% sodium deoxycholate/0.1% NaDodSO4) at 4°C. Labeled cell lysates were cleared by repeated absorption on Staphylococcus aureus and nonimmune serum. Equal amounts of radioactive protein were immunoprecipitated with specific antibodies. Antigen-antibody complexes were Abbreviations: Ab-MuLV and Mo-MuLV, Abelson and Moloney strains of murine leukemia virus; SV40, simian virus 40; bp, base pair(s); kb, kilobase(s).
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