dgn-np:NP557327.RANedefjFp2qqSrXDRPIg3qtgNf6i_pdyRICCADo0IBS8130_provenance { dgn-np:NP557327.RANedefjFp2qqSrXDRPIg3qtgNf6i_pdyRICCADo0IBS8130_assertiondcterms:description "[Our very recent assessment of the mechanisms by which cancer-associated increased lipogenesis and its inhibition alters the E2/ER signaling discovered that fatty acid synthase (FASN), the enzyme catalyzing the terminal steps in the de novo biosynthesis of long-chain fatty acids, differentially modulates the state of sensitivity of breast and endometrial cancer cells to E2-stimulated ER transcriptional activation and E2-dependent cell growth and survival: 1) pharmacological inhibition of FASN activity induced a dramatic augmentation of E2-stimulated ER-driven gene transcription, whereas interference (RNAi)-mediated silencing of FAS gene expression drastically lowered E2 requirements for optimal activation of ER transcriptional activation in breast cancer cells; conversely, pharmacological and RNAi-induced inhibition of FASN worked as an antagonist of E2- and tamoxifen-dependent ER transcriptional activity in endometrial adenocarcinoma cells; 2) pharmacological and RNAi-induced inhibition of FASN synergistically enhanced E2-mediated down-regulation of ER protein and mRNA expression in breast cancer cells, whereas specific FASN blockade resulted in a marked down-regulation of E2-stimulated ER expression in endometrial cancer cells; and 3) FASN inhibition decreased cell proliferation and cell viability by promoting apoptosis in hormone-dependent breast and endometrial cancer cells.]. Sentence from MEDLINE/PubMed, a database of the U.S. National Library of Medicine."@en ; wi:evidencedgn-void:source_evidence_literature ; sio:SIO_000772miriam-pubmed:16809439 ; prov:wasDerivedFromdgn-void:befree-2016 ; prov:wasGeneratedByeco:ECO_0000203 . dgn-void:befree-2016pav:importedOn "2016-02-19"^^xsd:date . dgn-void:source_evidence_literatureaeco:ECO_0000212 ; rdfs:comment "Gene-disease associations inferred from text-mining the literature."@en ; rdfs:label "DisGeNET evidence - LITERATURE"@en . }