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Expression of the forkhead transcription factor FOXL2 correlates with good prognosis in breast cancer patients treated with tamoxifen
Örebro University, School of Health and Medical Sciences.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.ORCID iD: 0000-0002-7498-7157
University of Skövde, Skövde, Sweden.
Örebro University Hospital, Örebro, Sweden.ORCID iD: 0000-0001-6881-237X
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2011 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 38, no 4, p. 1145-1151Article in journal (Refereed) Published
Abstract [en]

Aromatase is an important enzyme in the local synthesis of oestrogens and its expression has been shown to be increased in breast cancer through the activation of multiple promoters. However, the mechanisms behind this are not yet fully understood. A novel candidate in this context is the transcription factor forkhead box L2 (FOXL2), which has been recognised to be co-expressed with aromatase and transcriptionally active promoter 11 in developing goat and chicken ovaries. We propose that FOXL2 could be involved in the increased expression of aromatase in breast cancer. We examined FOXL2 and its relation to aromatase in 132 postmenopausal breast cancer patients by immunohistochemistry. Using in silico analysis, we further searched for FOXL2 binding-elements in the aromatase gene promoters. The results demonstrate that FOXL2 is expressed in breast cancer and influences clinical outcome with improved recurrence-free survival in cases with nuclear expression. In a multivariate Cox model, nuclear FOXL2 was a significant prognostic factor in ER-positive patients treated with tamoxifen (HR=0.18, 95% confidence interval (CI)=0.04-0.81, P=0.03). Tumours expressing nuclear FOXL2 were also more likely positive for stromal and/or cytoplasmic aromatase (P=0.03 and P=0.008, respectively). In silico analyses revealed binding elements of FOXL2 in promoters 1.3, 11 and 17 of the aromatase gene of which promoter 1.7 was most significant. In conclusion, this is the first study to report that FOXL2 is expressed in breast cancer and correlates with aromatase as well as with clinical outcome. The results further strengthen a possible binding of FOXL2 to aromatase promoter 1.7. Nevertheless, whether FOXL2 is a direct activator of aromatase requires further investigation.

Place, publisher, year, edition, pages
2011. Vol. 38, no 4, p. 1145-1151
Keywords [en]
breast cancer, forkhead box L2, aromatase, tissue specific promoters, in silico
National Category
Cancer and Oncology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-16840DOI: 10.3892/ijo.2011.923ISI: 000288581100027PubMedID: 21271216Scopus ID: 2-s2.0-79952329924OAI: oai:DiVA.org:oru-16840DiVA, id: diva2:438405
Available from: 2011-09-02 Created: 2011-09-02 Last updated: 2018-05-03Bibliographically approved
In thesis
1. Biological profiles of endocrine breast cancer
Open this publication in new window or tab >>Biological profiles of endocrine breast cancer
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Örebro: Örebro university, 2015. p. 82
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 123
Keywords
Endocrine breast cancer, tamoxifen, Foxl2, Wwox, ErbB4, HER4, gene expression, randomized patients
National Category
Cancer and Oncology
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-43963 (URN)978-91-7529-071-3 (ISBN)
Public defence
2015-05-29, Universitetssjukhuset, Wilandersalen, Södra Grev Rosengatan, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Funder
Swedish Cancer SocietyCancer and Allergy Foundation
Note

Funding: Magnus Bergvall Cancer Foundation; Percy Falk foundation for research in breast and prostate cancer; Nyckelfonden; Örebro University Hospital; Lions cancer research foundation, Region Uppsala-Örebro

Available from: 2015-03-30 Created: 2015-03-30 Last updated: 2017-10-17Bibliographically approved

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Wegman, PiaGöthlin Eremo, AnnaKarlsson, Mats G.Wingren, Sten

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Wegman, PiaGöthlin Eremo, AnnaKarlsson, Mats G.Wingren, Sten
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International Journal of Oncology
Cancer and Oncology

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