Medical College of Wisconsin
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Budesonide exerts its chemopreventive efficacy during mouse lung tumorigenesis by modulating gene expressions. Oncogene 2004 Oct 07;23(46):7746-52 PMID: 15361829

Pubmed ID

15361829

Abstract

Budesonide, a glucocorticoid, was proven to be a highly effective agent in preventing the development of lung tumors in A/J mice. In a lung tumor bioassay, budesonide produced 70% inhibition of tumor multiplicity and 94% reduction of total tumor load compared to benzopyrene (B[a]P) treated mice. Gene expression array analysis was performed on mouse lung tumors from this bioassay using Affymetrix U74Av2 GeneChips to determine gene expression changes associated with budesonide treatment. We found 363 genes that were changed between lung tumors induced by treatment with B[a]P and similar tumors treated with budesonide. Among them, 243 genes were overexpressed and 120 genes were underexpressed after budesonide treatment. In addition, 108 genes differentially expressed during mouse lung tumorigenesis (50 genes overexpressed and 58 genes underexpressed) were modulated back to normal levels after budesonide treatment when compared with the controls group. These genes are involved in a broad range of different pathways including control of cell cycle, signal transduction, and apoptosis and may play a role in the observed preventive effect. Our results suggest that budesonide exerts its effects of chemoprevention through growth arrest via Mad2/3 and through apoptosis via Bim/Blk and, by inference, caspase-8/9. Using the pathway visualization tool GenMapp, G protein pathway and MAPK cascade were also regulated by budesonide. Thus, we have determined, for the first time, the expression profiles of genes modulated by budesonide during murine lung tumorigenesis. Our results indicate that the chemopreventive effects of budesonide in the mouse lung tumorigenesis assay involved increase and decrease expression of a wide variety of genes in multiple signaling pathways.

Author List

Yao R, Wang Y, Lemon WJ, Lubet RA, You M

Author

Ming You MD, PhD Associate Provost, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




Scopus

2-s2.0-7044247179   38 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Anticarcinogenic Agents
Budesonide
Cell Cycle Proteins
Gene Expression Regulation, Neoplastic
Lung Neoplasms
Mice
Signal Transduction
Transcription Factors
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e