Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perfluorooctanoic acid (PFOA) is a common environmental pollutant that has been associated with various diseases, including cancer. We explored the molecular mechanisms underlying PFOA-induced endometrial cancer cell invasion and migration. PFOA treatment enhanced migration and invasion by human Ishikawa endometrial cancer cells, which correlated with decreased E-cadherin expression, a marker of epithelial-mesenchymal transition. PFOA also induced activation of ERK1/2/mTOR signaling. Treatment with rapamycin, an mTOR inhibitor, antagonized the effects of PFOA and reversed the effects of PFOA activation in a xenograft mouse model of endometrial cancer. Consistent with these results, pre-treatment with rapamycin abolished PFOA-induced down-regulation of E-cadherin expression. These results indicate that PFOA is a carcinogen that promotes endometrial cancer cell migration and invasion through activation of ERK/mTOR signaling.
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PMID:Perfluorooctanoic acid induces human Ishikawa endometrial cancer cell migration and invasion through activation of ERK/mTOR signaling. 2758 85

Perfluorooctanoic acid (PFOA) is a persistent organic pollutant prevalent in the environment and implicated in damage to the liver leading to a fatty liver phenotype called hepatocellular steatosis. Our goal is to provide a basis for PFOA-induced hepatocellular steatosis in relation to epigenetic alterations and mRNA splicing. Young adult female mice exposed to different concentrations of PFOA showed an increase in liver weight with decreased global DNA methylation (5-mC). At higher concentrations, the expression of DNA methyltransferase 3A (Dnmt3a) was significantly reduced and the expression of tet methycytosine dioxygenase 1 (Tet1) was significantly increased. There was no significant change in the other Dnmts and Tets. PFOA exposure significantly increased the expression of cell cycle regulators and anti-apoptotic genes. The expression of multiple genes involved in mTOR (mammalian target of rapamycin) signaling pathway were altered significantly with reduction in Pten (phosphatase and tensin homolog, primary inhibitor of mTOR pathway) expression. Multiple splicing factors whose protein but not mRNA levels affected by PFOA exposure were identified. The changes in protein abundance of the splicing factors was also reflected in altered splicing pattern of their target genes, which provided new insights on the previously unexplored mechanisms of PFOA-mediated hepatotoxicity and pathogenesis.
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PMID:Effect of PFOA on DNA Methylation and Alternative Splicing in Mouse Liver. 3232 Jul 74