This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE) prepared this text

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Sample pooling can be a powerful, cost-effective, and rapid means of identifying the most common changes in a gene expression profile. We identified osteopontin as a clinically useful marker of tumor progression by use of gene expression profiling on pooled samples.

BackgroundColon cancer has been classically described by clinicopathologic features that permit the prediction of outcome only after surgical resection and staging.MethodsWe performed an unsupervised analysis of microarray data from 326 colon cancers to identify the first principal component (PC1) of the most variable set of genes. PC1 deciphered two primary, intrinsic molecular subtypes of colon cancer that predicted disease progression and recurrence.ResultsHere we report that the most dominant pattern of intrinsic gene expression in colon cancer (PC1) was tightly correlated (Pearson R = 0.92, P < 10-135) with the EMT signature-- both in gene identity and directionality. In a global micro-RNA screen, we further identified the most anti-correlated microRNA with PC1 as MiR200, known to regulate EMT.ConclusionsThese data demonstrate that the biology underpinning the native, molecular classification of human colon cancer--previously thought to be highly heterogeneous-- was clarified through the lens of comprehensive transcriptome analysis.

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This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE) prepared this text

No abstract

We have investigated the regulation of p27 kip1 , a cyclin-dependent kinase inhibitor, in BALB/c 3T3 cells during growth factor-stimulated transition from quiescence (G 0 ) to a proliferative (G 1 ) state. The level of p27 kip1 protein falls dramatically after mitogenic stimulation and is accompanied by a decrease in cyclin E associated p27 kip1, as well as a transient increase in cyclin D1-associated p27 kip1 that later declines concomitantly with the loss of total p27 kip1 . Analysis of metabolically labelled cells revealed that cyclin D2, cyclin D3, and cdk4 were also partnered with p27 kip1 in quiescent BALB/c 3T3 cells and that this association decreased after platelet-derived growth factor (PDGF) treatment. Furthermore, the decline in p27 kip1 and reduced association with cyclin D3, initiated by the addition of PDGF but not plasma-derived factors, suggested that these changes are involved in competence, the first step in the exit from G 0 . Synthesis of p27 kip1 as determined by incorporation of [ 35 S]methionine was repressed upon mitogenic stimulation, and PDGF was sufficient to elicit this repression within 2 to 3 h. Pulse-chase experiments demonstrated the reduced rate of synthesis was not the result of an increased rate of degradation. Full repression of p27 kip1 synthesis required the continued presence of PDGF and failed to occur in the presence of the RNA polymerase inhibitor 5,6-dichlorobenzimidazole riboside. These characteristics demonstrate that repression was a late effect of PDGF and was consistent with our finding that conditional expression of activated H-ras did not affect synthesis of p27 kip1. Northern (RNA) analysis of p27 kip1 mRNA revealed that the repression was not accompanied by a corresponding decrease in p27 kip1 mRNA, suggesting that the PDGF-regulated decrease in p27 kip1 expression occurred through a translational mechanism.Under normal circumstances, proliferation of mammalian cells is a highly controlled process. This control is achieved, in part, by growth factors and cytokines that exert either mitogenic and/or antiproliferative effects in a cell-specific manner (1). Binding of growth-regulatory ligands results in the activation of signaling pathways that trigger direct alteration of specific metabolic pathways as well as immediate and delayed changes in gene expression (65). Mitogenic stimulation initiates a program of sequential synthesis of proteins, termed cyclins, that complex with and activate cyclin-dependent kinases (cdks) (9, 29-31, 39, 52, 54, 64, 67), enzymes that modulate key regulatory events leading to progression through and transitions between different stages of the cell cycle (7,13,20,21,47,55,64). The order of cyclin synthesis during cell cycle traverse has been examined in a variety of cells, including T cells, macrophages, epithelial cells, and fibroblasts (16,30,31,44,45,50,52). The D-type cyclins, which complex with cdk4 and cdk6, are the first cyclins synthesized during the cell cycle. They are detected in mid-G 1 and are believed to function as Rb ...