Matches in SemOpenAlex for { <https://semopenalex.org/work/W3020829665> ?p ?o ?g. }
Showing items 1 to 72 of
72
with 100 items per page.
- W3020829665 endingPage "905" @default.
- W3020829665 startingPage "905" @default.
- W3020829665 abstract "3927 The serin/threonine kinase Akt/Protein kinase B (PKB) is a key regulator of the phosphatidylinositol 3-kinase pathway and plays a critical role in controlling the balance between cell survival and apoptosis. Upon activation, Akt delivers survival signals by inhibiting pro-apoptotic molecules such as Bad, Caspase-9, IkB kinase (IKK) and forkhead transcription factors. Several reports implicated Akt/PKB in the molecular pathogenesis of different human malignancies. Overexpression of Akt/PKB was recently demonstrated to be an early event in colorectal carcinogenesis. In the course of analysing the molecular effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on different cancer cell lines we observed that the Akt/PKB protein level is reduced in response to aspirin. Expression profiling of aspirin treated colon cancer cells using oligonucleotide microarrays and quantitative real time RT-PCR revealed that expression of Akt1 but not that of its isoforms Akt2 and 3 was downregulated within 24 hours upon treatment. Interestingly, Akt-downregulation thereby ran parallel to aspirin-induced inhibition of Wnt/beta-Catenin signalling. To further elucidate the regulation of Akt expression in colon cancer cells we generated reporter constructs containing the luciferase gene under control of the Akt1 promoter region. By database analysis of the genomic sequence we identified 9 putative beta-Catenin/TCF binding elements within 2200 bp upstream of the transcription start site of the Akt1 gene. Accordingly, we hypothesized that the Akt1 gene might be regulated by the Wnt/beta-Catenin pathway. Transient expression of different reporter constructs containing Akt1 promoter regions revealed that the Akt1 promoter is stimulated in colorectal cancer cell lines harbouring constitutively activated Wnt-signalling. Luciferase expression was stimulated 5-fold in SW948 cells and 20-fold in HCT116 cells. In contrast, the promoter construct showed only a weak response in 293 embryonic kidney cells. By co-expression of a constitutive active beta-Catenin mutant the activation was further enhanced, indicating beta-Catenin/TCF dependent transcription of the Akt1 gene in colon cancer cells. In addition, immunohistochemical staining of tumor sections derived from colorectal cancer patients revealed elevated expression levels of Akt1, correlating with enhanced nuclear expression of beta-Catenin. In summary we propose that Akt1 is directly regulated by beta-Catenin. Since activation of the Akt kinase in turn leads to stabilization and accumulation of beta-Catenin, this might result in an autocrine loop reducing the response to apoptotic stimuli." @default.
- W3020829665 created "2020-05-13" @default.
- W3020829665 creator A5007438121 @default.
- W3020829665 creator A5031409922 @default.
- W3020829665 creator A5038944818 @default.
- W3020829665 creator A5079885079 @default.
- W3020829665 date "2004-04-01" @default.
- W3020829665 modified "2023-09-26" @default.
- W3020829665 title "Regulation of Akt/PKB expression in colorectal cancer cells" @default.
- W3020829665 hasPublicationYear "2004" @default.
- W3020829665 type Work @default.
- W3020829665 sameAs 3020829665 @default.
- W3020829665 citedByCount "0" @default.
- W3020829665 crossrefType "journal-article" @default.
- W3020829665 hasAuthorship W3020829665A5007438121 @default.
- W3020829665 hasAuthorship W3020829665A5031409922 @default.
- W3020829665 hasAuthorship W3020829665A5038944818 @default.
- W3020829665 hasAuthorship W3020829665A5079885079 @default.
- W3020829665 hasConcept C137620995 @default.
- W3020829665 hasConcept C153911025 @default.
- W3020829665 hasConcept C154137905 @default.
- W3020829665 hasConcept C154779307 @default.
- W3020829665 hasConcept C185592680 @default.
- W3020829665 hasConcept C502942594 @default.
- W3020829665 hasConcept C62478195 @default.
- W3020829665 hasConcept C75217442 @default.
- W3020829665 hasConcept C86554907 @default.
- W3020829665 hasConcept C86803240 @default.
- W3020829665 hasConcept C88216763 @default.
- W3020829665 hasConcept C95444343 @default.
- W3020829665 hasConceptScore W3020829665C137620995 @default.
- W3020829665 hasConceptScore W3020829665C153911025 @default.
- W3020829665 hasConceptScore W3020829665C154137905 @default.
- W3020829665 hasConceptScore W3020829665C154779307 @default.
- W3020829665 hasConceptScore W3020829665C185592680 @default.
- W3020829665 hasConceptScore W3020829665C502942594 @default.
- W3020829665 hasConceptScore W3020829665C62478195 @default.
- W3020829665 hasConceptScore W3020829665C75217442 @default.
- W3020829665 hasConceptScore W3020829665C86554907 @default.
- W3020829665 hasConceptScore W3020829665C86803240 @default.
- W3020829665 hasConceptScore W3020829665C88216763 @default.
- W3020829665 hasConceptScore W3020829665C95444343 @default.
- W3020829665 hasLocation W30208296651 @default.
- W3020829665 hasOpenAccess W3020829665 @default.
- W3020829665 hasPrimaryLocation W30208296651 @default.
- W3020829665 hasRelatedWork W1793257384 @default.
- W3020829665 hasRelatedWork W1972256954 @default.
- W3020829665 hasRelatedWork W1983972170 @default.
- W3020829665 hasRelatedWork W2004307711 @default.
- W3020829665 hasRelatedWork W2019898510 @default.
- W3020829665 hasRelatedWork W2035019079 @default.
- W3020829665 hasRelatedWork W2069439270 @default.
- W3020829665 hasRelatedWork W2110164171 @default.
- W3020829665 hasRelatedWork W2110678035 @default.
- W3020829665 hasRelatedWork W2111336104 @default.
- W3020829665 hasRelatedWork W2118257218 @default.
- W3020829665 hasRelatedWork W2120316083 @default.
- W3020829665 hasRelatedWork W2158582892 @default.
- W3020829665 hasRelatedWork W2380028180 @default.
- W3020829665 hasRelatedWork W2416681354 @default.
- W3020829665 hasRelatedWork W2469417466 @default.
- W3020829665 hasRelatedWork W2800827202 @default.
- W3020829665 hasRelatedWork W3130764299 @default.
- W3020829665 hasRelatedWork W3158743587 @default.
- W3020829665 hasRelatedWork W3204118135 @default.
- W3020829665 hasVolume "64" @default.
- W3020829665 isParatext "false" @default.
- W3020829665 isRetracted "false" @default.
- W3020829665 magId "3020829665" @default.
- W3020829665 workType "article" @default.