Dissection of transcriptional programmes in response to serum and c-Myc in a human B-cell line.
Proliferation of higher eukaryotic cells is triggered by the proto-oncogene c-myc (myc), which is induced downstream of a large number of growth factor receptors. Myc, a basic helix-loop-helix leucine zipper transcription factor, transmits growth signals by up- and downregulation of target genes. The importance of Myc in growth control is well established. However, the number of growth control genes requiring Myc as an essential factor for regulation after mitogenic stimulation of cells is not yet clear. Here, we have studied the transcriptional programme of a human B-cell line, P493-6, in response to Myc and serum. P493-6 cells do not express the endogenous myc, nor is it induced by serum stimulation. Proliferation of the cells is dependent upon both the expression of a tetracycline-regulated myc gene and serum stimulation. Using DNA microarrays, expression profiling was performed following stimulation of cells with serum, with Myc, or with both. We observed serum regulation of >1000 genes. A number of these genes were synergistically or antagonistically regulated by Myc. Moreover, we identified >300 Myc-regulated genes that were almost unresponsive to serum. Gene ontology analysis revealed that a high proportion of Myc target genes are involved in ribosome biogenesis and tRNA metabolism. The data support our current notion that Myc is essential for the regulation of a large number of growth-related genes in B cells, and cannot be replaced by other serum-induced factors.
Schlosser
Isabel
I
GSF Research Centre, Institute of Clinical Molecular Biology and Tumour Genetics, Marchioninistr. 25, D-81377 Munich, Germany.
Hölzel
Michael
M
Hoffmann
Reinhard
R
Burtscher
Helmut
H
Kohlhuber
Franz
F
Schuhmacher
Marino
M
Chapman
Rob
R
Weidle
Ulrich H
UH
Eick
Dirk
D
D001402:B-Lymphocytes; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D003470:Culture Media; D016259:Genes, myc; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*
D003470:Culture Media; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc