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Ligand activation of peroxisome proliferator-activated receptor induces γ apoptosis of leukemia cells by down-regulating the c-myc gene expression via blockade of the Tcf-4 activity.
- Source :
- Cell Death & Differentiation; May2002, Vol. 9 Issue 5, p513, 14p
- Publication Year :
- 2002
-
Abstract
- The peroxisome proliferator-activated receptor γ (PPAR γ), a member of the nuclear receptor superfamily, is expressed at highest levels in adipose tissue and functions as a central regulator in the process of adipocyte differentiation. In the present study, we showed that human leukemic cell lines, not only myeloid but also lymphoid, express PPAR γ and its activation by natural ligand (15-deoxy-δ[sup 12,14]-prostaglandin J2) and synthetic ligand (troglitazone) profoundly inhibited their proliferation by induction of apoptosis preferentially in the serum-free culture. We pursued its mechanism using the representative cell lines, and found that induction of apoptosis was accompanied by caspase-3 activation and specifically blocked by its inhibitor. While status of several apoptosisrelated molecules remained unchanged, the c-Myc expression was markedly down-regulated within 24 h after troglitazone treatment. The c-myc mRNA levels were dramatically reduced at 1 h and became undetectable at 12 h after troglitazone treatment, which proved to be accompanied by complete blockade of the Tcf-4 activity in the electrophoretic mobility shift assay. We succeeded in establishing HL-60 cell lines growing well in the presence of troglitazone in the long-term serum-free culture. They showed neither induction of apoptosis nor down-regulation of the c-Myc expression via blockade of the Tcf-4 activity after troglitazone treatment. This is the first identification of the linkage between PPAR γ-mediated apoptosis and down-regulation of the c-myc gene expression. [ABSTRACT FROM AUTHOR]
- Subjects :
- APOPTOSIS
LEUKEMIA
CANCER cells
LIGANDS (Biochemistry)
Subjects
Details
- Language :
- English
- ISSN :
- 13509047
- Volume :
- 9
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Cell Death & Differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 8649318
- Full Text :
- https://doi.org/10.1038/sj.cdd.4401000