Expression of the forkhead transcription factor FOXL2 correlates with good prognosis in breast cancer patients treated with tamoxifen

  • Authors:
    • Pia Wegman
    • Anna Göthlin Eremo
    • Angelica Lindlöf
    • Mats Karlsson
    • Olle Stål
    • Sten Wingren
  • View Affiliations

  • Published online on: Monday, January 24, 2011
  • Pages: 1145-1151
  • DOI: 10.3892/ijo.2011.923

Abstract

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 II 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 post-menopausal 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 I.3, II and I.7 of the aromatase gene of which promoter I.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 I.7. Nevertheless, whether FOXL2 is a direct activator of aromatase requires further investigation.
Journal Cover

April 2011
Volume 38 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
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APA
Wegman, P., Göthlin Eremo, A., Lindlöf, A., Karlsson, M., Stål, O., & Wingren, S. (2011). Expression of the forkhead transcription factor FOXL2 correlates with good prognosis in breast cancer patients treated with tamoxifen. International Journal of Oncology, 38(4), 1145-1151.
MLA
Wegman, Göthlin Eremo, Lindlöf, Karlsson, Stål, and Sten Wingren. "Expression of the forkhead transcription factor FOXL2 correlates with good prognosis in breast cancer patients treated with tamoxifen." International Journal of Oncology International Journal of Oncology 38.4 (2011): 1145-1151.
Chicago
Wegman, Göthlin Eremo, Lindlöf, Karlsson, Stål, and Sten Wingren. "Expression of the forkhead transcription factor FOXL2 correlates with good prognosis in breast cancer patients treated with tamoxifen." International Journal of Oncology International Journal of Oncology 38 no. 4 (2011): 1145-1151.