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Identification of c-myc responsive genes using rat cDNA microarray
1Molecular Signaling and Oncogenesis Section, Department of Cancer and Cell Biology, Medicine Branch, Division of Clinical Science, National Cancer Institute, Bethesda, Maryland 20892, USA.
Abstract:
c-Myc functions through direct activation or repression of transcription. Using cDNA microarray analysis, we have identified c-Myc-responsive genes by comparing gene expression profiles between c-myc null and c-myc wild-type rat fibroblast cells and between c-myc null and c-myc null cells reconstituted with c-myc. From a panel of 4400 cDNA elements, we found 198 genes responsive to c-myc when comparing wild-type or reconstituted cells with the null cells. The plurality of the named c-Myc-responsive genes that were up-regulated, including 30 ribosomal protein genes, are involved in macromolecular synthesis and metabolism, suggesting a major role of c-Myc in the regulation of protein synthetic and metabolic pathways. When ectopically overexpressed, c-Myc induced a different and smaller set of c-Myc-responsive genes as compared with the physiologically expressed c-Myc condition. Thus, these results from expression profiling suggest a new primary function for c-Myc and raise the possibility that the physiological and transforming functions of c-myc may be separable.
Insights
The study identified 198 genes responsive to c-Myc, highlighting its role in regulating macromolecular synthesis and metabolism. This suggests distinct physiological and transforming functions for c-Myc.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- c-Myc is a transcription factor regulating gene expression.
- Understanding c-Myc's targets is crucial for deciphering its role in cellular processes.
Purpose of the Study:
- To identify genes directly regulated by c-Myc.
- To investigate the role of c-Myc in regulating macromolecular synthesis and metabolism.
- To explore potential differences between physiological and ectopic c-Myc functions.
Main Methods:
- cDNA microarray analysis was used to compare gene expression profiles.
- Gene expression was analyzed in c-myc null and wild-type rat fibroblast cells.
- Gene expression was also compared in reconstituted c-myc null cells versus null cells.
Main Results:
- 198 out of 4400 cDNA elements were found to be responsive to c-Myc.
- Upregulated c-Myc-responsive genes included 30 ribosomal protein genes, involved in synthesis and metabolism.
- Ectopic overexpression of c-Myc affected a different, smaller set of genes compared to physiological expression.
Conclusions:
- c-Myc plays a significant role in regulating protein synthesis and metabolic pathways.
- Physiological and transforming functions of c-myc may be separable based on distinct gene expression profiles.
- Expression profiling reveals a potential new primary function for c-Myc.