PMID: 9163103Jan 1, 1996Paper

The effect of the tumor suppressor p53 and its mutant forms on the differentiation and viability of K562 leukemic cells

Tsitologiia
O S KremenetskaiaBoris P Kopnin

Abstract

Mutations of the p53 tumor suppressor are often observed in various human malignancies including blast crisis of chronic myelogenous leukaemia (CML). The pattern of p53 mutation in CML shows some peculiarities as compared with the majority of other neoplasias. In particular, the substitutions at codon 273, one of the most common p53 alteration in various tumors, are not characteristic of CML. To test whether distinction in the pattern of p53 mutation are associated with certain peculiarities of biological effects of different mutant proteins in myeloid cells, we obtained and analysed a panel of human K562 cell sublines expressing various exogenous p53: human Pro156, His175, His194, Trp248 and His 273, or murine temperature-sensitive (ts) Val135 that has properties of mutant protein at 37 degrees C, but shows activities of wild-type (wt) p53 at 32 degrees C. We have found that expression of wt-p53 enhanced the dependence of cells on growth/survival factors, incubation of sparse (< 10(5) cells per/ml) K562/Val135 cultures at 32 degrees C caused apoptosis. In media conditioned by cells of different origin (K562, colorectal carcinoma LIM 1215, Rat1 fibroblast) the p53-dependent apoptosis was inhibited. In conditions that do not lea...Continue Reading

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