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Gene expression profiles of proliferating vs. G1/G0 arrested human leukemia cells suggest a mechanism for glucocorticoid‐induced apoptosis
Author(s) -
TONKO MARTIN,
AUSSERLECHNER MICHAEL J.,
BERNHARD DAVID,
HELMBERG ARNO,
KOFLER REINHARD
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0327com
Subject(s) - biology , apoptosis , cell cycle , glucocorticoid receptor , gene expression , microbiology and biotechnology , programmed cell death , gene , cdk inhibitor , cell growth , transcription factor , cancer research , cyclin dependent kinase , genetics
Glucocorticoids (GC) have pronounced effects on metabolism, differentiation, proliferation, and cell survival (1). In certain lymphocytes and lymphocyte‐related malignancies, GC inhibit proliferation and induce apoptotic cell death, which has led to their extensive use in the therapy of malignant lymphoproliferative disorders (2). Most of these effects result from regulation of gene expression via the GC receptor (GR), a ligand‐activated transcription factor (3). Although hundreds of genes are regulated by GC (1), how certain biological GC effects relate to individual gene regulation remains enigmatic. To address this question with respect to GC‐induced cell cycle arrest and apoptosis, we applied DNA chip technol¬ogy (4, 5) to determine gene expression profiles in proliferating and G1/G0‐arrested (by conditional expres¬sion of the CDK inhibitor p16/INK4a) acute lymphoblas¬tic Τ cells undergoing GC‐induced apoptosis. Of 7074 genes tested, 163 were found to be regulated by dexamethasone in the first 8 h in proliferating cells and 66 genes in G1/G0‐arrested cells. An almost nonoverlapping set of genes (i.e., only eight genes) was coordinately regulated in proliferating and arrested cells. Analysis of the regulated genes supports the concept that GC‐induced apoptosis results from positive GR autoregulation entail¬ing persistent down‐regulation of metabolic pathways crit¬ical for survival.—Tonko, M., Ausserlechner, M. J., Bernhard, D., Helmberg, A., Kofler, R. Gene expression profiles of proliferating vs. G1/G0 arrested human leu¬kemia cells suggest a mechanism for glucocorticoid‐induced apoptosis. FASEB J. 15, 693‐699 (2001)