Overproduction of p53 antigen makes established cells highly tumorigenic

Abstract

The p53 cellular tumour antigen, long known to be overproduced in a variety of neoplastically transformed cells, was recently shown to be directly involved in transformation. Thus, p53 can complement activated Ha-ras in transforming secondary rat embryo fibroblasts into grossly altered, tumorigenic cells. Moreover, p53 can also be shown to possess immortalizing activity. Our previous results indicated, however, that the contribution of p53 to the transformation was not synonymous with immortalization, suggesting that the two activities of the protein are probably separable. We demonstrate here that this is indeed the case, as overproduction of p53 in an established cell line, while not causing gross morphological changes, endows these cells with an overt tumorigenic potential. Furthermore, the tumorigenic efficiency of such cell lines may be correlated with the extent of p53 over-production.

Transcription regulation by mutant p53

“…Exogenous expression of cloned TP53 was shown to immortalize cells (Jenkins et al, 1984) and endow them with overt tumorigenic potential in mice Eliyahu et al, 1985). Furthermore, cloned TP53 could co-operate with Ha-ras to transform normal rat embryonic fibroblasts (Eliyahu et al, 1984;Parada et al, 1984).…”

Cytoplasmic retention of mutant tsp53 is dependent on an intermediate filament protein (Vimentin) scaffold

“…The expression vector D61 codes for a vimentin protein lacking AS 50 ± 104 of the head domain. Expression of the murine tsp53 Val135 was based on the eukaryotic expression vector pLTRcG9 (Eliyahu et al, 1985).…”

Testicular wild-type p53 expression in transgenic mice induces spermiogenesis alterations ranging from differentiation defects to apoptosis

“…This plasmid was cut by AatII and SalI to generate a 2185 bp fragment, and by AatII and XhoI to yield a 2502 bp fragment including the p53 cDNA (sequences 1 to 159) downstream of pMT-I. Both fragments were ligated with a XhoI ± SalI digest of LTRp53cG ala plasmid containing the genomic sequences of wtp53 and the polyadenylation site of SV40 (generously provided by Dr Oren) (Eliyahu et al, 1985). The resulting plasmid was designated MTmp53cG ala .…”