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Titolo:
RESISTANCE OF HUMAN LEUKEMIC CEM-C1 CELLS IS OVERCOME BY SYNERGISM BETWEEN GLUCOCORTICOID AND PROTEIN-KINASE-A PATHWAYS - CORRELATION WITH C-MYC SUPPRESSION
Autore:
MEDH RD; SAEED MF; JOHNSON BH; THOMPSON EB;
Indirizzi:
UNIV TEXAS,MED BRANCH,DEPT HUMAN BIOL CHEM & GENET GALVESTON TX 77555 UNIV TEXAS,MED BRANCH,DEPT HUMAN BIOL CHEM & GENET GALVESTON TX 77555
Titolo Testata:
Cancer research
fascicolo: 16, volume: 58, anno: 1998,
pagine: 3684 - 3693
SICI:
0008-5472(1998)58:16<3684:ROHLCC>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE LYMPHOBLASTIC-LEUKEMIA; T-LYMPHOMA-CELLS; CYCLIC-AMP; INDUCED APOPTOSIS; RECEPTOR EXPRESSION; STEROID ANTAGONIST; CYTOLYTIC RESPONSE; MESSENGER-RNA; REH CELLS; GENE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
62
Recensione:
Indirizzi per estratti:
Citazione:
R.D. Medh et al., "RESISTANCE OF HUMAN LEUKEMIC CEM-C1 CELLS IS OVERCOME BY SYNERGISM BETWEEN GLUCOCORTICOID AND PROTEIN-KINASE-A PATHWAYS - CORRELATION WITH C-MYC SUPPRESSION", Cancer research, 58(16), 1998, pp. 3684-3693

Abstract

Glucocorticoids (GCs) induce apoptosis in lymphoid cells that containfunctional GC receptors (GRs). However, GC resistance often is seen in cells with demonstrable GRs; one such line is CEM-C1. We have testedthe hypothesis that positive interactions between GC and cyclic AMP (cAMP) regulate GC actions in CEM clones. Treatment of both GC-resistant CEM-CI [resistant to 1 mu M dexamethasone (Dex)] and the sensitive sister clone, CEM-C7 (similar to 65% cell death with 20 nhl Dex, similar to 99% death with 1 mu M Dex), with a less than or equal to 20 mu M concentration of the protein kinase A activator, forskolin, had no significant effect on cell viability. Cotreatment with Dex and forskolin resulted in a strong synergistic death response, with only similar to 10% CEM-C1 cells surviving treatment with 1 phl Dex and 20 mu M forskolin, This death was blocked by the GR antagonist RU 38486. However, the extent of apoptosis did not correlate with the amount of GR protein or binding activity in either C7 or C1 cells. As reported previously, Dex-evoked cell death was associated with suppression of c-Myc in C7 cells. In CEM-C1 cells, Dex alone did not affect c-Myc; however, Dex plus forskolin suppressed c-Myc levels, To evaluate mechanisms of Dex-forskolin synergism, fresh subclones of CEM-C7 (clone 14) and CEM-CI (clone 15) were isolated, to ensure purity of phenotype. In these, forskolin (with or without Dex) caused a similar increase in cAMP (similar to 300-fold) and phospho-cAMP-responsive element binding protein (similar to 4-5-fold) levels, whereas total cAMP-responsive element binding protein expression was not affected. GR transcription function, as tested from a GR-responsive 330-bp mouse mammary tumor virus promoter-luciferase reporter construct, was induced 8- and 4-fold by 1 mu M Dex treatment of CEM-C7 14 and CEM-C1-15 cells, respectively. Forskolin (10 mu M) significantly potentiated Dex response in CEM-C1-15 cells (13.5-fold) but had only a modest effect (1.5-fold) in CEM-C7-14 cells. These studies suggest that sensitization of CEM-CI cells by cross-talk between GR and protein kinase A pathways may occur via cooperative effects on GR-mediated gene transcription.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 21:27:08