Expression profiling of glucocorticoid-treated T-ALL cell lines: rapid repression of multiple genes involved in RNA-, protein- and nucleotide synthesis.
To arrive at a better understanding of the effects of the glucocorticoid component of chemotherapy protocols on lymphocytic leukemia cells, we analysed early responses of T-lymphocytic leukemia cell lines Jurkat and CEM-C7, both of which undergo apoptosis in response to dexamethasone, via gene chips. Among genes identified as repressed, a notable cluster seemed to be of importance for the processes of transcription, mRNA splicing and protein synthesis. Consequently, we assessed time-resolved uptake of uridine and methionine to monitor RNA and protein synthesis, along with parameters quantifying apoptosis. Repression of uptake to about 65% of that in untreated cells preceded the first sign of apoptosis by several hours in both cell lines. In addition to this general repression of RNA and protein synthesis, several genes were found to be regulated that may contribute to synergistic action of glucocorticoids with other components of frequently used chemotherapy protocols such as antimetabolites, methotrexate and alkylating agents.
Obexer
P
P
Institute of Pathophysiology, University of Innsbruck, Medical School, A 6020 Innsbruck, Austria.
Certa
U
U
Kofler
R
R
Helmberg
A
A
D017209:Apoptosis; D004273:DNA, Neoplasm / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis / Q000187:drug effects; D012326:RNA Splicing / Q000187:drug effects; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D005938:Glucocorticoids; D012334:RNA, Neoplasm; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone