Journal article
Global gene expression profiling in mouse plasma cell tumor precursor and bystander cells reveals potential intervention targets for plasma cell neoplasia
Blood, Vol.119(4), pp.1018-1028
01/26/2012
DOI: 10.1182/blood-2011-06-363887
PMCID: PMC3271714
PMID: 22147894
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 oil granulomas (OG) isolated from IP pristane-injected BALB/c.iMyc
Eμ
mice at 5 different time points during tumor progression. We used laser capture microdissection 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 used ANOVA and Bayesian estimation of temporal regulation. 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 down-regulation) of the Spp1/osteopontin-dependent network and up-regulation of mRNA translation/protein synthesis. The latter led to a biologic validation study that showed that the AMPK-activating diabetes drug, metformin, was a potent specific PCT inhibitor in vitro.
Details
- Title: Subtitle
- Global gene expression profiling in mouse plasma cell tumor precursor and bystander cells reveals potential intervention targets for plasma cell neoplasia
- Creators
- Jason LeGrand - Molecular Genetics Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; andEun Sung Park - Molecular Genetics Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; andHongyang Wang - Molecular Genetics Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; andShalu Gupta - Molecular Genetics Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; andJames D Owens - Molecular Genetics Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; andPatrick J Nelson - Molecular Genetics Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; andWendy DuBois - Molecular Genetics Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; andThomas Bair - Holden Comprehensive Cancer Center andSiegfried Janz - Holden Comprehensive Cancer Center andJ. Frederic Mushinski - Molecular Genetics Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; and
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.119(4), pp.1018-1028
- Publisher
- American Society of Hematology
- DOI
- 10.1182/blood-2011-06-363887
- PMID
- 22147894
- PMCID
- PMC3271714
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Grant note
- National Institutes of Health
- Language
- English
- Date published
- 01/26/2012
- Academic Unit
- Pathology
- Record Identifier
- 9984083220702771
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