Rearrangements of the cellular p53 gene in erythroleukaemic cells transformed by Friend virus

Abstract

There is now good evidence that the cellular protein, p53, is involved in the transformation process, although its precise role is unknown. It was reported recently that expression of the p53 gene can immortalize cells and that the p53 gene can replace the myc oncogene in a myc-ras immortalization/transformation assay. We have investigated whether p53 is involved in the progression towards the neoplastic state in vivo and report here that erythroleukaemic cell lines transformed by different isolates of Friend leukaemia virus show altered expression of the cellular p53 gene. High levels of p53 protein are found in certain lines, but the protein is undetectable in others. This heterogeneity in p53 gene expression is associated with heterogeneity in tumorigenicity. We demonstrate that genomic rearrangements are responsible for p53 gene inactivation in these cell lines and that they occur in vivo during the natural progression of Friend virus-induced erythroleukaemia.

Twenty years of p53 research: structural and functional aspects of the p53 protein

“…This conclusion was based on the ®nding that rearrangement and functional inactivation of p53 gene was observed at high frequency in mouse spleen tumours induced by the Friend erythroleukaemia virus (Mowat et al, 1985;Chow et al, 1987;Rovinsky et al, 1987;Ben David et al, 1988;Munroe et al, 1988).…”

Transcription regulation by mutant p53

“…In parallel, evidence was obtained showing inactivation of the TP53 gene in transformed lymphoid cell lines induced by Ab-MuLV virus. Likewise, TP53 gene inactivation and frequent rearrangements were shown in mouse spleen tumors induced by the Friend erythroleukaemia virus (Mowat et al, 1985;Chow et al, 1987;Munroe et al, 1988), strongly suggesting that p53 inactivation, rather than excessive p53 activation, might promote transformation.…”

Alteration of p73 in acute myelogenous leukemia

“…Moreover, point mutations in p73 may not be the only way to abrogate or compromise p73 function. For example, p53 structure and functions can be altered by conformational changes in the p53 protein, slicing abnormalities, viral protein binding, and upregulation of intrinsic proteins such as MDM-2 [29][30][31][32][33][34][35]. Thus the absence of p73 coding mutations does not exclude p73 from playing a role in AML.…”