Analysis of gene expression patterns during glucocorticoid-induced apoptosis using oligonucleotide arrays.
To determine the genes responsible for mediating the effects of glucocorticoids (GCs) on leukemic cells, transcriptional changes in GC-sensitive human pre-B leukemia 697 cells during GC-induced apoptosis were monitored using oligonucleotide microarrays. To circumvent the challenge of recovering mRNAs from dying cells, we compared the pattern of gene expression with that of 697 cells protected from apoptosis by transfection with bcl-2. Of the 12,000 genes examined for their response to GC, 93 genes were induced and 28 genes were repressed, many of which are known to be implicated in signal transduction, growth arrest, and transcription. These included the signal transduction-related genes encoding SOCS1, SOCS2, FKBP51, DSCR1, p56lck, and four protein kinase phosphatases. Growth arrest-related genes encoding p19(INK4d) and several Myc inhibitors were induced in response to the GC treatment. Anti-proliferative- or apoptosis-related genes encoding BTG1, BTG2, and granzyme A were also found to be transcriptionally up-regulated by GC. In addition, the regulation of genes encoding the glucocorticoid receptor and steroid receptor coactivator-1 suggested autoregulation of a GC-mediated signaling pathway.
Yoshida
Ning Lu
NL
Genox Research, Inc., Teikyo University Biotech Center, 907 Nogawa, Miyamae, Kawasaki, Kanagawa 216-0001, Japan.
Miyashita
Toshiyuki
T
U
Mami
M
Yamada
Masao
M
Reed
John C
JC
Sugita
Yuji
Y
Oshida
Tadahilo
T
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002470:Cell Survival; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D005434:Flow Cytometry; D015870:Gene Expression; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D009355:Neomycin / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D018931:Antineoplastic Agents, Hormonal; D005938:Glucocorticoids; D011500:Protein Synthesis Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012313:RNA; D003907:Dexamethasone; D004247:DNA; D009355:Neomycin