Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Unravelingthe molecular mechanism behind metabolic reprogramming caused by alterations of the enzyme PI3-kinase
University of Skövde, School of Bioscience.
2019 (English)Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
Abstract [en]

Oncogenes and tumor suppressor genes play a key role in cancer induction and progression. They directly or indirectly regulate critical metabolic pathways, phosphatidylinositol-3 kinase pathway being frequently activated pathway in cancer. The catalytic subunit of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), p110α, is the most frequently mutated kinase in human cancer, E542K, E545K, and H1047R mutations being the most common. Expression of hepatic E545K and H1047R p110α mutants in vivo shows marked and rapid increase in hepatic lipid and glycogen accumulation in mice with developmental (chronic) liver-specific deletion of p110α, which was not seen in mice when wildtype p110α is overexpressed. To investigate the logical pathways that could explain the lipid accumulation in mutant expressing mice, RNA sequencing from wildtype, knockout and mutated mouse livers was performed. Read alignment and count quantification was done using the Rsubread package and the statistical analyses are performed using the DeSeq2 package. Differentially expressed genes were identified with adjusted p-value of 0.05. Gene ontology analysis was performed on the differentially expressed genes using clusterProfiler, an R package to identify several key pathways which were upregulated and downregulated among the different sample groups. Signaling pathways related to cell cycle processes were mainly upregulated in the mutated samples when compared with the wildtype as well as knockout samples while signaling pathways related to many metabolic processes seem to be downregulated in mutated samples, even though these mutants showed upregulated metabolism by accumulation of lipids and glycogen physiologically. To confirm the results of gene expression data the results have to be cross validated with the gold standard quantitative Real Time Polymerase Chain Reaction.

Place, publisher, year, edition, pages
2019. , p. [60]
National Category
Medical Bioscience
Identifiers
URN: urn:nbn:se:his:diva-17410OAI: oai:DiVA.org:his-17410DiVA, id: diva2:1335888
Subject / course
Systems Biology
Educational program
Tumor Biology - Master’s Programme
Supervisors
Examiners
Available from: 2019-09-12 Created: 2019-07-08 Last updated: 2019-09-12Bibliographically approved

Open Access in DiVA

fulltext(2397 kB)4 downloads
File information
File name FULLTEXT01.pdfFile size 2397 kBChecksum SHA-512
29232fc28fa18aeae9c9a8b6474da03f3faf7793f2a634c3ab9a9ca54ce1754b848a5f6af41fba5cb116fc2f0e73c22936c2c7181df064a829fc2018880d44db
Type fulltextMimetype application/pdf

Search in DiVA

By author/editor
Patel, Angana Heet
By organisation
School of Bioscience
Medical Bioscience

Search outside of DiVA

GoogleGoogle Scholar
Total: 4 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

urn-nbn

Altmetric score

urn-nbn
Total: 80 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf