PTPN2 deficiency along with activation of nuclear Akt predict endocrine resistance in breast cancerShow others and affiliations
2019 (English)In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 145, no 3, p. 599-607Article in journal (Refereed) Published
Abstract [en]
Purpose The protein tyrosine phosphatase, non-receptor type 2 (PTNP2) regulates receptor tyrosine kinase signalling, preventing downstream activation of intracellular pathways like the PI3K/Akt pathway. The gene encoding the protein is located on chromosome 18p11; the 18p region is commonly deleted in breast cancer. In this study, we aimed to evaluate PTPN2 protein expression in a large breast cancer cohort, its possible associations to PTPN2 gene copy loss, Akt activation, and the potential use as a clinical marker in breast cancer. Methods PTPN2 protein expression was analysed by immunohistochemistry in 664 node-negative breast tumours from patients enrolled in a randomised tamoxifen trial. DNA was available for 146 patients, PTPN2 gene copy number was determined by real-time PCR. Results PTPN2 gene loss was detected in 17.8% of the tumours. Low PTPN2 protein expression was associated with higher levels of nuclear-activated Akt (pAkt-n). Low PTPN2 as well as the combination variable low PTPN2/high pAkt-n could be used as predictive markers of poor tamoxifen response. Conclusion PTPN2 negatively regulates Akt signalling and loss of PTPN2 protein along with increased pAkt-n is a new potential clinical marker of endocrine treatment efficacy, which may allow for further tailored patient therapies.
Place, publisher, year, edition, pages
SPRINGER , 2019. Vol. 145, no 3, p. 599-607
Keywords [en]
TCPTP; 18p deletion; PTPN2; Protein tyrosine phosphatase; Breast cancer; Gene copy number; Immunohistochemistry
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-154985DOI: 10.1007/s00432-018-2810-6ISI: 000459180600006PubMedID: 30515568OAI: oai:DiVA.org:liu-154985DiVA, id: diva2:1297561
Note
Funding Agencies|Swedish Cancer Society; Cancer Research Foundations of Radiumhemmet; Cancer Society in Stockholm; King Gustav V Jubilee Clinical Research Foundation; ALF grants Region Ostergotland; Onkologiska Klinikernas i Linkoping Forskningsfond
2019-03-202019-03-202020-04-28