Global Gene Expression Profiling in Mouse Plasma Cell Tumor Precursor and Bystander Cells Reveals Potential Intervention Targets for Plasma-Cell Neoplasia
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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. Laser capture micro-dissection was used to collect incipient PCT cells and their global gene expression analyzed on Affymetrix Mouse Genome 430A microarrays.
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. 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. To read the article in full, please click on the link provided.