Gene networks in glucocorticoid-evoked apoptosis of leukemic cells.
To discover the genes responsible for the apoptosis evoked by glucocorticoids in leukemic lymphoid cells, we have begun gene array analysis on microchips. Three clones of CEM cells were compared: C7-14, C1-15 and C1-6. C7-14 and C1-15 are subclones from the original clones C7 (sensitive to apoptosis by glucocorticoids) and C1 (resistant). C1-6 is a spontaneous revertant to sensitivity from the C1 clone. Previously we presented data on the sets of genes whose expression is altered in these cell clones after 20 h exposure to dexamethasone (Dex). The two sensitive clones, which respond by undergoing apoptosis starting about 24h after Dex is added, both showed >2.5-fold induction of 39 genes and 2-fold reduction of expressed levels from 21 genes. C1-15, the resistant clone, showed alterations in a separate set of genes. In this paper, we present further analysis of the data on genes regulated in these cell clones after 20 h Dex and compare them with the genes regulated after 12h Dex. Some, but not all the genes found altered at 20 h are altered at 12h, consistent with our hypothesis that sequential gene regulation eventually provokes full apoptosis. We also compare the levels of basal gene expression in the three clones. At the basal level no single gene stands out, but small sets of genes differ >2-fold in basal expression between the two sensitive and the resistant clone. A number of the genes basally higher in the resistant clone are potentially anti-apoptotic. This is consistent with our hypothesis that the resistant cells have undergone a general shift in gene expression.
Webb
M Scott
MS
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0645, USA.
Miller
Aaron L
AL
Johnson
Betty H
BH
Fofanov
Yuriy
Y
Li
Tongbin
T
Wood
Thomas G
TG
Thompson
E Brad
EB
D017209:Apoptosis / Q000235:genetics*; D002999:Clone Cells; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D003907:Dexamethasone