Abstract
The c-Myb, A-Myb and B-Myb transcription factors have nearly identical DNA-binding domains, activate the same reporter gene constructs in animal cells, but have different biological roles. The Myb proteins are often coexpressed in the same cells, raising questions about whether they activate similar or distinct gene expression profiles, and whether they cooperate or compete in regulating the same promoters. Here, recombinant adenoviruses were used to express each protein in human mammary cells, and then microarray assays were used to assess global changes in gene expression. Each Myb protein induced a unique and specific set of changes, displaying activities far more complex than revealed by standard reporter gene assays. These results have important implications for the roles of various Myb proteins in normal and transformed human cells, for regulatory pathways that might modify their activities and for the importance of acquired mutations that may qualitatively alter their functions in tumors.
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Acknowledgements
We thank Jessica Burns, who provided outstanding technical assistance. This research was supported by grants to SAN from the USPHS/National Cancer Institute (#RO1 CA58443) and The Human Frontiers Science Program (#RG0358/1999M) and by institutional support from the University of New Mexico Health Sciences Center (RAC and HHMI #4-11347). JJR was supported in part by a young investigator grant from the American Cancer Society (IRG no. 192), awarded to the UNM Cancer Research and Treatment Facility. The microarray experiments were performed using facilities in the Keck-UNM Genomics Resource and the UNM Cancer Research and Treatment Center. Complete sets of microarray data can be obtained by contacting S Ness (ness@unm.edu).
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Rushton, J., Davis, L., Lei, W. et al. Distinct changes in gene expression induced by A-Myb, B-Myb and c-Myb proteins. Oncogene 22, 308–313 (2003). https://doi.org/10.1038/sj.onc.1206131
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DOI: https://doi.org/10.1038/sj.onc.1206131
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