liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • 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
FOXO3a: a novel player in thyroid carcinogenesis?
Division of Endocrinology and Diabetes, Department of Internal Medicine, University of Leipzig, Ph.-Rosenthal-Street 27, 04103 Leipzig, Germany.
Division of Endocrinology and Diabetes, Department of Internal Medicine, University of Leipzig, Ph.-Rosenthal-Street 27, 04103 Leipzig, Germany.
Division of Endocrinology and Diabetes, Department of Internal Medicine, University of Leipzig, Ph.-Rosenthal-Street 27, 04103 Leipzig, Germany.
Institute of Pathology and Neuropathology, University of Duisburg-Essen, Essen, Germany.
Show others and affiliations
2009 (English)In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 16, no 1, 189-99 p.Article in journal (Refereed) Published
Abstract [en]

The forkhead box transcription factor FOXO3a has recently been identified as central mediator of the cellular response to oxidative stress inducing cell cycle arrest or apoptosis. The aim of our study was to investigate the regulation of FOXO3a in the thyroid and to determine whether alterations in FOXO3a activity occur in thyroid carcinogenesis. In vitro, we demonstrate that FOXO3a activity is negatively regulated by the PI3K/Akt cascade promoting increased phosphorylation and cytoplasmatic accumulation of FOXO3a with decreased transcription of the target genes p27kip (CDKN1B) and Bim (BCL2L11), but increased expression of GADD45A. By contrast, we show that H(2)O(2) exposure activates FOXO3a in thyrocytes with JNK (MAPK8)-mediated nuclear accumulation of FOXO3a and increased expression of the cell cycle arrest genes p27kip and GADD45A. In vivo, we observed a marked cytoplasmatic accumulation of FOXO3a in differentiated thyroid cancers versus an exclusive nuclear accumulation in follicular adenoma and normal thyroid tissue. Moreover, this cytosolic accumulation of FOXO3a correlated with an increased phospho-Akt expression in thyroid malignancies and was accompanied by decreased expression of the FOXO targets p27kip and Bim and an increase in GADD45A mRNA expression in the thyroid cancers. Our data suggest FOXO3a as a novel player of cellular stress response in the thyroid, mediating the thyrocyte's fate either to survive or to undergo apoptosis. Furthermore, PI3K-dependent FOXO3a inactivation may be a novel pathomechanism for the escape from apoptosis in thyroid cancer cells, in particular in follicular thyroid carcinoma.

Place, publisher, year, edition, pages
2009. Vol. 16, no 1, 189-99 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-101885DOI: 10.1677/ERC-07-0283PubMedID: 18845647OAI: oai:DiVA.org:liu-101885DiVA: diva2:666780
Available from: 2013-11-24 Created: 2013-11-24 Last updated: 2017-12-06

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Gimm, Oliver

Search in DiVA

By author/editor
Gimm, Oliver
In the same journal
Endocrine-Related Cancer
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 31 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • 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