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
Loss of protein tyrosine phosphatase, non-receptor type 2 is associated with activation of AKT and tamoxifen resistance in breast cancer
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
Show others and affiliations
2015 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 153, no 1, 31-40 p.Article in journal (Refereed) Published
Abstract [en]

Breast cancer is a heterogeneous disease and new clinical markers are needed to individualise disease management and therapy further. Alterations in the PI3K/AKT pathway, mainly PIK3CA mutations, have been shown frequently especially in the luminal breast cancer subtypes, suggesting a cross-talk between ER and PI3K/AKT. Aberrant PI3K/AKT signalling has been connected to poor response to anti-oestrogen therapies. In vitro studies have shown protein tyrosine phosphatase, non-receptor type 2 (PTPN2) as a previously unknown negative regulator of the PI3K/AKT pathway. Here, we evaluate possible genomic alterations in the PTPN2 gene and its potential as a new prognostic and treatment predictive marker for endocrine therapy benefit in breast cancer. PTPN2 gene copy number was assessed by real-time PCR in 215 tumour samples from a treatment randomised study consisting of postmenopausal patients diagnosed with stage II breast cancer 1976-1990. Corresponding mRNA expression levels of PTPN2 were evaluated in 86 available samples by the same methodology. Gene copy loss of PTPN2 was detected in 16 % (34/215) of the tumours and this was significantly correlated with lower levels of PTPN2 mRNA. PTPN2 gene loss and lower mRNA levels were associated with activation of AKT and a poor prognosis. Furthermore, PTPN2 gene loss was a significant predictive marker of poor benefit from tamoxifen treatment. In conclusion, genomic loss of PTPN2 may be a previously unknown mechanism of PI3K/AKT upregulation in breast cancer. PTPN2 status is a potential new clinical marker of endocrine treatment benefit which could guide further individualised therapies in breast cancer.

Place, publisher, year, edition, pages
Springer Verlag (Germany) , 2015. Vol. 153, no 1, 31-40 p.
Keyword [en]
18p; AKT; Breast cancer; Endocrine resistance; Phosphatases; PTPN2
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-121133DOI: 10.1007/s10549-015-3516-yISI: 000359775100005PubMedID: 26208487OAI: oai:DiVA.org:liu-121133DiVA: diva2:852293
Note

Funding Agencies|Swedish Cancer Society [13 0435]; Swedish Research Council [A0346701]

Available from: 2015-09-08 Created: 2015-09-08 Last updated: 2017-12-04

Open Access in DiVA

fulltext(646 kB)77 downloads
File information
File name FULLTEXT01.pdfFile size 646 kBChecksum SHA-512
2be513b9cfa3a742d51e697b76350b815dab133e03a367f6330d6cca4e83dbcdadeb89a35b7933bc0d61be58121fef7b2fa702e8bc9ed170aae1b67a5dc3b238
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Karlsson, ElinVeenstra, CynthiaPerez-Tenorio, GizehNordenskjöld, BoStål, Olle

Search in DiVA

By author/editor
Karlsson, ElinVeenstra, CynthiaPerez-Tenorio, GizehNordenskjöld, BoStål, Olle
By organisation
Division of Clinical SciencesFaculty of Medicine and Health SciencesDepartment of OncologyDepartment of Oncology
In the same journal
Breast Cancer Research and Treatment
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar
Total: 77 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

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 154 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