Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Improvements in detection, treatment and prognosis for patients with non-small cell lung cancer (NSCLC) depend on the molecular understanding of tumor development and progression. Using Affymetrix GeneChips comprising 59,620 elements, we determined the gene expression profiles of 89 NSCLC and 15 normal lung samples. We found 187 (0.3%) genes, which are at least 2-fold overexpressed and 157 (0.3%) genes 2-fold less expressed in NSCLC compared with normal lung. Cell cycle regulation, cell adhesion and nucleotide metabolism were the major biological processes connected to a large proportion of genes up-regulated in NSCLC. Down-regulated genes were frequently involved in metabolic/catabolic processes and signal transduction. The expression of specific genes revealed reliable differentiation of tumor from normal lung tissues, as well as the classification of both NSCLC subtypes squamous cell carcinoma and adenocarcinoma. In this context, collagens (COL7, 17) and cytokeratins (CK6, 15, 17) are preferentially induced in squamous cell carcinoma, whereas several transcription factors (TTF1, DAT1, TF-2) are exclusively elevated in adenocarcinomas. Some gene products involved in the metastatic process [matrixmetalloproteinase 12 (MMP-12) and urokinase plasminogen activator alpha (uPA)] were found as prognostic markers for the recurrence free interval and survival. Particularly, the simultaneous use of the MMP-12 and uPA expression predicted relapse-free and global survival of the patients. Screening of NSCLC with a genome-wide array revealed diagnostic, prognostic and potential therapeutic targets that might be suitable for an individual risk profile by tumor specific arrays.
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PMID:Identification and classification of differentially expressed genes in non-small cell lung cancer by expression profiling on a global human 59.620-element oligonucleotide array. 1686 60

In the present work we used a murine mammary cancer model of two related adenocarcinomas with different lung metastasizing abilities, to compare their global gene expression profiles. Clontech Atlas mouse cDNA microarrays of primary cultured tumor cells were employed to identify genes that are modulated in the more metastatic variant MM3 relative to its parental tumor M3. A total of 88 from 1,176 genes were differentially expressed in MM3 primary cultures, most of them (n=86) were upregulated. Genes were grouped according to their functions as associated with signal transduction and transcription regulation (e.g. Stat1 and Zfp 92), with cell adhesion and motility (cadherin 1, fibronectin), with invasion and angiogenesis (uPA, 72 kDa MMP2), with the regulation of cell proliferation and cell death (cyclins G and A2, TNF), and also included growth factors and receptors, oncogenes and tumor suppressors genes (p107, TGFbeta2, TBR-I, PDGFR). Only 2 genes, TTF1 and fibronectin (FN), showed a significant downregulation. Notably FN expression, loss of which has been associated with a malignant phenotype, was reduced about 19-fold in the more metastatic MM3 cells. Previously known differences in expression patterns associated with the metastatic capacity of MM3 and M3 adenocarcinomas, including downregulation of FN or upregulated expression of TGFbeta and proteases, were confirmed by the array data. The fact that FN was one of the only two genes significantly down-regulated out of the 1,176 genes analyzed stresses the hypothesis that FN may behave as an important metastasis suppressor gene in mammary cancer.
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PMID:Fibronectin is distinctly downregulated in murine mammary adenocarcinoma cells with high metastatic potential. 1708 68