Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mantle cell lymphoma (MCL) is a non-Hodgkin's lymphoma of B-cell lineage. The blastoid variant of MCL, characterized by high mitotic rate, is clinically more aggressive than common MCL. We used the cDNA array technology to examine the gene expression profiles of both blastoid variant and common MCL. The data was analysed by regression analysis, principal component analysis and the naive Bayes' classifier. Eight genes were identified as differentially deregulated between the two groups. Oncogenes CMYC, BCL2 and PIM1 were upregulated more frequently in the blastoid variant than in common MCL. This implied that the gp130-mediated signal transducer and activator of transcription 3 (STAT3) signalling pathway was involved in the blastoid variant transformation of MCL. Other differentially deregulated genes were TOP1, CD23, CD45, CD70 and NFATC. By using the eight differentially deregulated genes, we created a classifier to distinguish the blastoid variant from common MCL with high accuracy. We also identified 18 genes that were deregulated in both groups. Among them, BCL1, CALLA/CD10 and GRN were suggested to be oncogenes. The products of RGS1, RGS2, ANX2 and CD44H were suggested to promote tumour metastasis. CD66D was suggested to be a tumour suppressor gene.
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PMID:Investigatory and analytical approaches to differential gene expression profiling in mantle cell lymphoma. 1247 67

Interleukin (IL)-6 family cytokines signal exclusively via the gp130 coreceptor, and are implicated in smoking-associated lung cancer, the most lethal cancer worldwide. However, the role of gp130 signalling pathways in transducing the carcinogenic effects of tobacco-related compounds is ill-defined. Here, we report that lung tumourigenesis induced by the potent tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (Nicotine-derived Nitrosamine Ketone; NNK) is suppressed in gp130(F/F) knock-in mice characterized by the contrasting gp130-dependant hypoactivation of extracellular signal-regulated kinase mitogen-activated protein kinase (ERK MAPK) and phosphatidylinositol 3-kinase/Akt, and hyperactivation of signal transducer and activator of transcription (STAT)3 signalling cascades. Specifically, in response to NNK, the absolute number and size of lung lesions in gp130(F/F) mice were significantly reduced compared with gp130(+/+) littermate controls, and associated with lower cellular proliferation without any alteration to the level of apoptosis in gp130(F/F) lung tumours. At the molecular level, reduced activation of ERK MAPK, but not Akt, was observed in lung tumours of gp130(F/F) mice, and corresponded with impaired expression of several tumour suppressor genes (for example, Trp53, Tsc2). Notably, STAT3 was not activated in the lungs of gp130(+/+) mice by NNK, and genetic normalization of STAT3 activation in gp130(F/F):Stat3(-/+) mice had no effect on NNK-induced tumourigenesis. The expression of tumour suppressor genes was reduced in tumours from current versus never-smoking lung cancer patients, and in vitro pharmacological inhibition of ERK MAPK signalling in human lung cancer cells abrogated NNK-induced downmodulation of tumour suppressor gene expression. Among IL-6 cytokine family members, IL-6 gene expression was specifically upregulated by NNK in vitro and in vivo, and inversely correlated with tumour suppressor gene expression. Collectively, our data reveal that a key molecular mechanism by which NNK promotes tumour cell proliferation during tobacco carcinogen-induced lung carcinogenesis is via upregulation of IL-6 and the preferential usage of gp130-dependant ERK MAPK signalling to downmodulate tumour suppressor gene expression.
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PMID:Differential involvement of gp130 signalling pathways in modulating tobacco carcinogen-induced lung tumourigenesis. 2472 95