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
ETS Factor ETV5 Activates the Mutant Telomerase Reverse Transcriptase Promoter in Thyroid Cancer
Royal North Shore Hosp, Australia; Univ Sydney, Australia.
Royal North Shore Hosp, Australia; Univ Sydney, Australia.
Royal North Shore Hosp, Australia.
Linköping University, Faculty of Medicine and Health Sciences. Royal North Shore Hosp, Australia.
Show others and affiliations
2019 (English)In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: Co-occurrence of TERT (telomerase reverse transcriptase) promoter (TERTp) mutations with BRAF/RAS mutations is associated with significantly more aggressive thyroid cancer. TERTp mutations are hypothesized to generate de novo binding sites for ETS transcription factors, which are themselves activated by BRAF/RAS-stimulated MEK-ERK activity. To date, a detailed study of this mechanism has been limited to only a few cancer types, and we hypothesized that ETS factors involved in TERTp activation could vary between different cancers. Methodology: Here we sought to identify ETS factor(s) required for TERTp activation in thyroid cancer, using a combination of in silico analyses of TCGA data, and experimentation using in vitro thyroid cell models analyzed by quantitative reverse transcription-PCR, immunoprecipitation (IP), chromatin IP, and gene reporter assays. Results: We found that ETV5 was abundantly expressed in papillary thyroid cancers from the TCGA data set, and in thyroid cancer cell line models. Furthermore, ETV5 was found to preferentially bind to the -124 bp(T) TERTp allele and stimulate TERT transcription in thyroid cancer cells devoid of GA binding protein transcription factor (GABP) activity. We also found that ETV5 functionally cooperates with the transcription factor FOXE1 to further enhance TERTp activity, a mechanism that may at least partially explain why FOXE1 represents a significant genetic determinant of thyroid cancer risk. Conclusions: ETS factors that activate mutant TERTp vary between cancer types, and here we show for the first time that ETV5 demonstrates mutant allele-specific affinity for TERTp in thyroid cancer, a property that has previously only been attributable to GABP.

Place, publisher, year, edition, pages
MARY ANN LIEBERT, INC , 2019.
Keywords [en]
thyroid cancer; TERT; ETS factors; MAPK
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:liu:diva-161842DOI: 10.1089/thy.2018.0314ISI: 000493187100001PubMedID: 31452441OAI: oai:DiVA.org:liu-161842DiVA, id: diva2:1370891
Note

Funding Agencies|Australian NHMRCNational Health and Medical Research Council of Australia [1061941]; Rebecca L. Cooper Medical Research Foundation

Available from: 2019-11-18 Created: 2019-11-18 Last updated: 2019-11-18

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Åberg, Helena
By organisation
Faculty of Medicine and Health Sciences
In the same journal
Thyroid
Endocrinology and Diabetes

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
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