Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular pathology of precursor lesions leading to invasive pancreatic ductal adenocarcinomas remains relatively unknown. We have applied cDNA microarray analysis to characterize gene expression profiles in a series of intraductal papillary-mucinous tumors (IPMTs) of the pancreas, which represents one of the alternative routes of intraepithelial progression to full malignancy in the pancreatic duct system. Using a cDNA microarray containing 4992 human genes, we screened a total of 13 IPMTs including nine noninvasive and four invasive cases. Expression change in more than half of the tumors was observed for 120 genes, ie, 62 up-regulated and 58 down-regulated genes. Some of the up-regulated genes in this study have been previously described in classical pancreatic carcinomas such as lipocalin 2, galectin 3, claudin 4, and cathepsin E. The most highly up-regulated genes in IPMTs corresponded to three members of the trefoil factor family (TFF1, TFF2, and TFF3). Immunohistochemistry performed on five genes found to be differentially expressed at the RNA level (TFF1, TFF2, TFF3, lipocalin 2, and galectin 3) showed a good concordance between transcript level and protein abundance, except for TFF2. Hierarchical clustering organized the cases according to the dysplastic and invasive phenotype of theIPMTs. This analysis has permitted us to implicate several genes (caveolin 1, glypican 1, growth arrest-specific 6 protein, cysteine-rich angiogenic inducer 61) in tumor progression. The observation that several genes are differentially expressed both in IPMTs and pancreatic carcinomas suggests that they may be involved at an early stage of pancreatic carcinogenesis.
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PMID:Characterization of gene expression profiles in intraductal papillary-mucinous tumors of the pancreas. 1627 14

Models of bladder tumor progression have suggested that genetic alterations may determine both phenotype and clinical course. We have applied expression microarray analysis to a divergent set of bladder tumors to further elucidate the course of disease progression and to classify tumors into more homogeneous and clinically relevant subgroups. cDNA microarrays containing 10,368 human gene elements were used to characterize the global gene expression patterns in 80 bladder tumors, 9 bladder cancer cell lines, and 3 normal bladder samples. Robust statistical approaches accounting for the multiple testing problem were used to identify differentially expressed genes. Unsupervised hierarchical clustering successfully separated the samples into two subgroups containing superficial (pT(a) and pT(1)) versus muscle-invasive (pT(2)-pT(4)) tumors. Supervised classification had a 90.5% success rate separating superficial from muscle-invasive tumors based on a limited subset of genes. Tumors could also be classified into transitional versus squamous subtypes (89% success rate) and good versus bad prognosis (78% success rate). The performance of our stage classifiers was confirmed in silico using data from an independent tumor set. Validation of differential expression was done using immunohistochemistry on tissue microarrays for cathepsin E, cyclin A2, and parathyroid hormone-related protein. Genes driving the separation between tumor subsets may prove to be important biomarkers for bladder cancer development and progression and eventually candidates for therapeutic targeting.
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PMID:Bladder cancer outcome and subtype classification by gene expression. 1593 Mar 39

The cathepsin family of lysosomal proteases is increasingly being recognized for their altered expression in cancer and role in facilitating tumor progression. The aspartyl protease cathepsin E is overexpressed in several cancers and has been investigated as a biomarker for pancreatic ductal adenocarcinoma (PDAC). Here we show that cathepsin E expression in mouse PDAC tumors is increased by more than 400-fold when compared to healthy pancreatic tissue. Cathepsin E accumulates over the course of disease progression and accounts for more than 3% of the tumor protein in mice with end-stage disease. Through immunoblot analysis we determined that only procathepsin E exists in mouse PDAC tumors and cell lines derived from these tumors. By decreasing the pH, this procathepsion E is converted to the mature form, resulting in an increase in proteolytic activity. Although active site inhibitors can bind procathepsin E, treatment of PDAC mice with the aspartyl protease inhibitor ritonavir did not decrease tumor burden. Lastly, we used multiplex substrate profiling by mass spectrometry to identify two synthetic peptides that are hydrolyzed by procathepsin E near neutral pH. This work represents a comprehensive analysis of procathepsin E in PDAC and could facilitate the development of improved biomarkers for disease detection.
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PMID:Procathepsin E is highly abundant but minimally active in pancreatic ductal adenocarcinoma tumors. 2714 1