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dc.contributor.author
Schmid, Christoph
dc.contributor.author
Ghirlanda, Claudia
dc.contributor.author
Niessen, Markus
dc.date.accessioned
2017-07-28T13:14:32Z
dc.date.available
2017-06-12T20:43:10Z
dc.date.available
2017-07-13T09:07:13Z
dc.date.available
2017-07-28T13:14:32Z
dc.date.issued
2017-08
dc.identifier.issn
0300-8177
dc.identifier.issn
1573-4919
dc.identifier.other
10.1007/s11010-017-2996-y
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/130191
dc.identifier.doi
10.3929/ethz-b-000130191
dc.description.abstract
Insulin controls blood glucose while insulin-like growth factor (IGF) 1 is an important growth factor. Interestingly, both hormones have overlapping bioactivities and can activate the same intracellular signal transduction cascades. Growth control (mainly by IGF1) and metabolic function (predominantly by insulin) are believed to depend on activation of extracellular signal-regulated kinases (ERKs) 1/2 and protein kinase B (Akt/PKB), respectively. Therefore, insulin analogues that are used to normalize blood glucose are tested for their ability to preferentially activate Akt/PKB but not ERK1/2 and mitogenesis. Growth hormone, IGF1, and hyperinsulinemia are associated with increased risk of growth progression of some cancer types. To test if continuous exposure to insulin can favour tumour growth, we studied insulin/IGF1-dependent activation of ERK1/2 and Akt/PKB by Western blotting, inhibition of apoptosis by ELISA, and induction of proliferation by [3H]-thymidine incorporation in Saos-2/B10 osteosarcoma cells. IGF1 and insulin both induced proliferation and prevented apoptosis effectively. Regulation of apoptosis was far more sensitive than regulation of proliferation. IGF1 and insulin activated PKB (Akt/PKB) rapidly and consistently maintained its phosphorylation. Activation of ERK1/2 was only observed in response to IGF1. Loss of p-Akt/PKB (but not of p-ERK1/2) was associated with increased apoptosis, and protection from apoptosis was lost when activation of Akt/PKB was inhibited. These findings in Saos-2/B10 cells were also replicated in the A549 cell line, originally derived from a human lung carcinoma. Therefore, IGF1 and insulin more likely (at lower concentrations) enhance tumour cell survival than proliferation, via activation and maintenance of phosphatidylinositol 3-kinase activity and p-Akt/PKB.
en_US
dc.language.iso
en
en_US
dc.publisher
Springer
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Apoptosis
en_US
dc.subject
IGF1
en_US
dc.subject
Insulin
en_US
dc.subject
Obesity
en_US
dc.subject
Osteosarcoma cells
en_US
dc.subject
PI3K
en_US
dc.title
Prevention of tumour cell apoptosis associated with sustained protein kinase B phosphorylation is more sensitive to regulation by insulin signalling than stimulation of proliferation and extracellular signal-regulated kinase
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2017-03-18
ethz.journal.title
Molecular and cellular biochemistry
ethz.journal.volume
432
en_US
ethz.journal.issue
1-2
en_US
ethz.journal.abbreviated
Mol. cell. biochem.
ethz.pages.start
41
en_US
ethz.pages.end
54
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.identifier.nebis
010838384
ethz.publication.place
Berlin
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2017-06-12T20:43:42Z
ethz.source
ECIT
ethz.identifier.importid
imp593655638803541489
ethz.ecitpid
pub:193193
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-28T13:14:37Z
ethz.rosetta.lastUpdated
2017-12-22T01:33:52Z
ethz.rosetta.versionExported
true
ethz.COinS
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