한빛사 논문
Abstract
Jason LeGrand1*, Eun Sung Park1*, Hongyang Wang1, Shalu Gupta1, James D. Owens Jr.1, Patrick J. Nelson1, Wendy DuBois1, Thomas Bair2, Siegfried Janz3, and J. Frederic Mushinski1,+
1 Molecular Genetics Section, Laboratory of Cancer Cell Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, United States;
2 Holden Comprehensive Cancer Center, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, United States;
3 Department of Pathology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, United States
* equal contribution
+ corresponding author
Abstract
Tumor progression usually proceeds through several sequential stages, any of which could be targets for interrupting the progression process if one understood these steps at the molecular level. We extracted nascent plasma cell tumor (PCT) cells from within inflammatory granulomas (OG) isolated from intraperitoneal pristane-injected BALB/c.iMycEμ mice at five different time points during tumor progression. We used laser capture micro-dissection to collect incipient PCT cells and analyzed their global gene expression on Affymetrix Mouse Genome 430A microarrays. Two independent studies were performed with different sets of mice. Analysis of the expression data employed Analysis of Variance (ANOVA) and Bayesian Estimation of Temporal Regulation (BETR). Genetic pathway analysis was performed using MetaCore (GeneGo) and IPA (Ingenuity). The gene expression profiles of PCT samples and those of undissected OG samples from adjacent sections showed that different genes and pathways were mobilized in the tumor cells during tumor progression, compared with their stroma. Our analysis implicated several genetic pathways in PCT progression, including biphasic (up- and then downregulation) of the Spp1/osteopontin-dependent network and upregulation of mRNA translation/protein synthesis. The latter led to a biological validation study that showed that the AMPK-activating diabetes drug, metformin, was a potent, specific PCT inhibitor, in vitro.
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