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p13α, a novel splice variant of PI3K 110α overexpressed in tumor, activated downstream Akt signaling, despite lacking a catalytic group
University of Skövde, School of Health Sciences.
2021 (English)Independent thesis Basic level (degree of Bachelor), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

The enzyme phosphoinositide 3-kinase (PI3K) with its catalytic subunit p110α is an important node in insulin signaling pathway and is the most frequently mutated enzyme in human cancer. A study has found a novel splice variant of p110α, the p13α, in colon tumor sample. Despite lacking the catalytic domain, it was still able to induce cell proliferation in vitro and activate the downstream target serine/threonine AKT. The aim of this project is to explain the molecular mechanisms behind the p13α properties. The p13α was introduced in Drosophila using HA-tag vector system under transcriptional control of UAS and da-gal4 and then induced by high and normal sugar diet. The hemolymph and protein was extracted from adult Drosophila and larvae. Western blot and protein expression study was performed on the Drosophila extracts as well as HEK293 cells transfected with p13α or the full length p110α. The p13α showed higher pCDC2 compared to the control and p110α samples. Cyclin A expression was increased in the p13α samples compared to the control and p110α samples. The p110α overexpressing samples showed weaker pWee compared to the p13α samples. In summary, despite lacking a catalytic domain, p13α still activates downstream AKT signaling and promote cell growth and proliferation through increased pCDC2, decreased pWee1 and increased Cyclin A synthesis. In conclusion, the activation of AKT by p13α is mediated through an unknown pathway and its investigation might lead to therapeutic inhibition of p13α oncogenic effect in Colon tumor.

Place, publisher, year, edition, pages
2021. , p. 29
National Category
Biomedical Laboratory Science/Technology
Identifiers
URN: urn:nbn:se:his:diva-19853OAI: oai:DiVA.org:his-19853DiVA, id: diva2:1567893
External cooperation
Sahlgrenska Academy at University of Gothenburg
Subject / course
Biomedicine/Medical Science
Educational program
Biomedicine - Study Programme
Supervisors
Examiners
Available from: 2021-06-16 Created: 2021-06-16 Last updated: 2021-06-16Bibliographically approved

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CiteExportLink to record
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Citation style
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