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Titolo:
P53-INDUCED APOPTOSIS IN THE HUMAN T-ALL CELL-LINE CCRF-CEM
Autore:
GELEY S; HARTMANN BL; HATTMANNSTORFER R; LOFFLER M; AUSSERLECHNER MJ; BERNHARD D; SGONC R; STRASSERWOZAK EMC; EBNER M; AUER B; KOFLER R;
Indirizzi:
INNSBRUCK UNIV,INST GEN & EXPT PATHOL,DIV MOL PATHOPHYSIOL A-6020 INNSBRUCK AUSTRIA INNSBRUCK UNIV,INST GEN & EXPT PATHOL,DIV MOL PATHOPHYSIOL A-6020 INNSBRUCK AUSTRIA INNSBRUCK UNIV,INST BIOCHEM A-6020 INNSBRUCK AUSTRIA
Titolo Testata:
Oncogene
fascicolo: 20, volume: 15, anno: 1997,
pagine: 2429 - 2437
SICI:
0950-9232(1997)15:20<2429:PAITHT>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLUCOCORTICOID-INDUCED APOPTOSIS; WILD-TYPE P53; P53-DEPENDENT APOPTOSIS; PROTEASE INHIBITORS; ICE/CED-3 PROTEASE; BREAST-CANCER; DNA-BINDING; DEATH; GENE; RESISTANCE;
Keywords:
P53; APOPTOSIS; CCRF-CEM; HUMAN LEUKEMIA; CASPASE; CHEMOTHERAPY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
72
Recensione:
Indirizzi per estratti:
Citazione:
S. Geley et al., "P53-INDUCED APOPTOSIS IN THE HUMAN T-ALL CELL-LINE CCRF-CEM", Oncogene, 15(20), 1997, pp. 2429-2437

Abstract

The tumor suppressor p53 has been implicated in apoptosis induction and is mutated in human T-ALL CCRF-CEM cells. To investigate possible consequences of wild-type p53 loss, we reconstituted CEM-C7H2, a subclone of CCRF-CEM, with a temperature-sensitive p53 allele (p53ts). Stably transfected lines expressed high levels of p53ts and shift to the permissive temperature (32 degrees C) caused rapid induction of p53-regulated genes, such as p21(CIP1/WAF1), mdm-2 and bax. This was followed by extensive apoptosis within 24 h to 36 h, supporting the notion thatmutational p53 inactivation contributed to the malignant phenotype. p53-dependent apoptosis was preceded by digestion of poly(ADP-ribose) polymerase, a typical target of interleukin-1 beta-converting enzyme (ICE)-like proteases/caspases, and was markedly resistant to the ICE/caspase-1 and FLICE/caspase-8 inhibitor acetyl-Tyr-Val-Afa-Asp.chloromethylketone (YVAD), but sensitive to the CPP32/caspase-3 inhibitor nzyloxycarbonyl-Asp-Glu-Val-Asp.fluoromethylketone (DEVD) and benzyloxycarbonyl-Val-Ala-Asp.fluoromethylketone (zVAD), a caspase inhibitor with broader specificity. This indicated an essential involvement of caspases, but argued against a significant role of ICE/caspase-1 or FLICE/caspase-8. Actinomycin D or cycloheximide prevented cell death, suggestingthat, in this system, p53-induced apoptosis depends upon macromolecule biosynthesis. Introduction of functional p53 into CEM cells enhancedtheir sensitivity to the DNA-damaging agent doxorubicin, but not to the tubulin-active compound vincristine. Thus, mutational p53 inactivation in ALL might entail relative resistance to DNA-damaging, but not to tubulin-destabilizing, chemotherapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/06/20 alle ore 07:41:09