FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2613973112> ?p ?o ?g. }

• W2613973112 endingPage "5097" @default.
• W2613973112 startingPage "5087" @default.
• W2613973112 abstract "MYC activation at modest levels has been frequently found in hepatocellular carcinoma. However, its significance in hepatocarcinogenesis has remained obscure. Here we examined the role of Myc activation in mouse liver tumours induced by hepatocytic expression of myristoylated AKT (AKT) and/or mutant HRASV12 (HRAS) via transposon-mediated gene integration. AKT or HRAS alone required 5 months to induce liver tumours, whereas their combination generated hepatocellular carcinoma within 8 weeks. Co-introduction of AKT and HRAS induced lipid-laden preneoplastic cells that grew into nodules composed of tumour cells with or without intracytoplasmic lipid, with the latter being more proliferative and associated with spontaneous Myc expression. AKT/HRAS-induced tumorigenesis was almost completely abolished when MadMyc, a competitive Myc inhibitor, was expressed simultaneously. The Tet-On induction of MadMyc in preneoplastic cells significantly inhibited the progression of AKT/HRAS-induced tumours; its induction in transformed cells suppressed their proliferative activity with alterations in lipid metabolism and protein translation. Transposon-mediated Myc overexpression facilitated tumorigenesis by AKT or HRAS, and when it was co-introduced with AKT and HRAS, diffusely infiltrating tumours without lipid accumulation developed as early as 2 weeks. Examination of the dose-responses of Myc in the enhancement of AKT/HRAS-induced tumorigenesis revealed that a reduction to one-third retained enhancing effect but three-times greater introduction damped the process with increased apoptosis. Myc overexpression suppressed the mRNA expression of proteins involved in the synthesis of fatty acids, and when combined with HRAS introduction, it also suppressed the mRNA expression of proteins involved in their degradation. Finally, the MYC-positive human hepatocellular carcinoma was characterized by the cytoplasm devoid of lipid accumulation, prominent nucleoli and a higher proliferative activity. Our results demonstrate that in hepatocarcinogenesis induced by both activated AKT and HRAS, activation of endogenous Myc is an enhancing factor and adequate levels of Myc deregulation further facilitate the process with alterations in cellular metabolism." @default.
• W2613973112 created "2017-05-19" @default.
• W2613973112 creator A5027558518 @default.
• W2613973112 creator A5036810926 @default.
• W2613973112 creator A5041369305 @default.
• W2613973112 creator A5042205540 @default.
• W2613973112 creator A5045329864 @default.
• W2613973112 creator A5048586536 @default.
• W2613973112 creator A5061160958 @default.
• W2613973112 creator A5068363630 @default.
• W2613973112 creator A5071859466 @default.
• W2613973112 creator A5084302861 @default.
• W2613973112 date "2017-05-08" @default.
• W2613973112 modified "2023-10-17" @default.
• W2613973112 title "Critical role of Myc activation in mouse hepatocarcinogenesis induced by the activation of AKT and RAS pathways" @default.
• W2613973112 cites W1492511624 @default.
• W2613973112 cites W1576881350 @default.
• W2613973112 cites W1919478107 @default.
• W2613973112 cites W1974911740 @default.
• W2613973112 cites W1975015168 @default.
• W2613973112 cites W1985122162 @default.
• W2613973112 cites W1985166341 @default.
• W2613973112 cites W1986730787 @default.
• W2613973112 cites W1988995126 @default.
• W2613973112 cites W1992581344 @default.
• W2613973112 cites W2011378554 @default.
• W2613973112 cites W2025073354 @default.
• W2613973112 cites W2031570299 @default.
• W2613973112 cites W2040235797 @default.
• W2613973112 cites W2042140414 @default.
• W2613973112 cites W2043395027 @default.
• W2613973112 cites W2045899555 @default.
• W2613973112 cites W2046405795 @default.
• W2613973112 cites W2048743409 @default.
• W2613973112 cites W2049509484 @default.
• W2613973112 cites W2054657650 @default.
• W2613973112 cites W2056794794 @default.
• W2613973112 cites W2072348418 @default.
• W2613973112 cites W2074648434 @default.
• W2613973112 cites W2082949384 @default.
• W2613973112 cites W2084780592 @default.
• W2613973112 cites W2093773860 @default.
• W2613973112 cites W2096455435 @default.
• W2613973112 cites W2103033431 @default.
• W2613973112 cites W2104630023 @default.
• W2613973112 cites W2114596030 @default.
• W2613973112 cites W2115141971 @default.
• W2613973112 cites W2125681624 @default.
• W2613973112 cites W2126410372 @default.
• W2613973112 cites W2130410032 @default.
• W2613973112 cites W2130410721 @default.
• W2613973112 cites W2138366746 @default.
• W2613973112 cites W2146915309 @default.
• W2613973112 cites W2152690616 @default.
• W2613973112 cites W2158378236 @default.
• W2613973112 cites W2161762726 @default.
• W2613973112 cites W2164618384 @default.
• W2613973112 cites W2169385554 @default.
• W2613973112 cites W2172697812 @default.
• W2613973112 cites W21751534 @default.
• W2613973112 cites W2218260032 @default.
• W2613973112 cites W2320147764 @default.
• W2613973112 cites W2337100437 @default.
• W2613973112 doi "https://doi.org/10.1038/onc.2017.114" @default.
• W2613973112 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5596209" @default.
• W2613973112 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28481866" @default.
• W2613973112 hasPublicationYear "2017" @default.
• W2613973112 type Work @default.
• W2613973112 sameAs 2613973112 @default.
• W2613973112 citedByCount "33" @default.
• W2613973112 countsByYear W26139731122017 @default.
• W2613973112 countsByYear W26139731122018 @default.
• W2613973112 countsByYear W26139731122019 @default.
• W2613973112 countsByYear W26139731122020 @default.
• W2613973112 countsByYear W26139731122021 @default.
• W2613973112 countsByYear W26139731122022 @default.
• W2613973112 countsByYear W26139731122023 @default.
• W2613973112 crossrefType "journal-article" @default.
• W2613973112 hasAuthorship W2613973112A5027558518 @default.
• W2613973112 hasAuthorship W2613973112A5036810926 @default.
• W2613973112 hasAuthorship W2613973112A5041369305 @default.
• W2613973112 hasAuthorship W2613973112A5042205540 @default.
• W2613973112 hasAuthorship W2613973112A5045329864 @default.
• W2613973112 hasAuthorship W2613973112A5048586536 @default.
• W2613973112 hasAuthorship W2613973112A5061160958 @default.
• W2613973112 hasAuthorship W2613973112A5068363630 @default.
• W2613973112 hasAuthorship W2613973112A5071859466 @default.
• W2613973112 hasAuthorship W2613973112A5084302861 @default.
• W2613973112 hasBestOaLocation W26139731121 @default.
• W2613973112 hasConcept C104317684 @default.
• W2613973112 hasConcept C1167327 @default.
• W2613973112 hasConcept C2781187634 @default.
• W2613973112 hasConcept C501734568 @default.
• W2613973112 hasConcept C502942594 @default.
• W2613973112 hasConcept C55493867 @default.
• W2613973112 hasConcept C555283112 @default.
• W2613973112 hasConcept C62478195 @default.
• W2613973112 hasConcept C75217442 @default.

• next