TY - JOUR
T1 - Wt-p53 action in human leukaemia cell lines corresponding to different stages of differentiation
AU - Rizzo, M. G.
AU - Zepparoni, A.
AU - Cristofanelli, B.
AU - Scardigli, R.
AU - Crescenzi, M.
AU - Blandino, G.
AU - Giuliacci, S.
AU - Ferrari, S.
AU - Soddu, S.
AU - Sacchi, A.
PY - 1998
Y1 - 1998
N2 - Recent studies support the potential application of the wt-p53 gene in cancer therapy. Expression of exogenous wt-p53 suppresses a variety of leukaemia phenotypes by acting on cell survival, proliferation and/or differentiation. As for tumour gene therapy, the final fate of the neoplastic cells is one of the most relevant points. We examined the effects of exogenous wt-p53 gene expression in several leukaemia cell lines to identify p53-responsive leukaemia. The temperature-sensitive p53(Val135) mutant or the human wt-p53 cDNA was transduced in leukaemia cell lines representative of different acute leukaemia FAB subtypes, including M1 (KG1), M2 (HL-60), M3 (NB4), M5 (U937) and M6 (HEL 92.1.7), as well as blast crisis of chronic myelogenous leukaemia (BC-CML: K562, BV173) showing diverse differentiation features. By morphological, molecular and biochemical analyses, we have shown that exogenous wt-p53 gene expression induces apoptosis only in cells corresponding to M1, M2 and M3 of the FAB classification and in BC-CML showing morphological and cytochemical features of undifferentiated blast cells. In contrast, it promotes differentiation in the others. Interestingly cell responsiveness was independent of the vector used and the status of the endogenous p53 gene.
AB - Recent studies support the potential application of the wt-p53 gene in cancer therapy. Expression of exogenous wt-p53 suppresses a variety of leukaemia phenotypes by acting on cell survival, proliferation and/or differentiation. As for tumour gene therapy, the final fate of the neoplastic cells is one of the most relevant points. We examined the effects of exogenous wt-p53 gene expression in several leukaemia cell lines to identify p53-responsive leukaemia. The temperature-sensitive p53(Val135) mutant or the human wt-p53 cDNA was transduced in leukaemia cell lines representative of different acute leukaemia FAB subtypes, including M1 (KG1), M2 (HL-60), M3 (NB4), M5 (U937) and M6 (HEL 92.1.7), as well as blast crisis of chronic myelogenous leukaemia (BC-CML: K562, BV173) showing diverse differentiation features. By morphological, molecular and biochemical analyses, we have shown that exogenous wt-p53 gene expression induces apoptosis only in cells corresponding to M1, M2 and M3 of the FAB classification and in BC-CML showing morphological and cytochemical features of undifferentiated blast cells. In contrast, it promotes differentiation in the others. Interestingly cell responsiveness was independent of the vector used and the status of the endogenous p53 gene.
KW - Apoptosis
KW - Differentiation
KW - Gene therapy
KW - Leukaemia
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=7144264382&partnerID=8YFLogxK
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M3 - Article
C2 - 9652758
AN - SCOPUS:7144264382
VL - 77
SP - 1429
EP - 1438
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 9
ER -