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Tamoxifen decreases extracellular TGF-beta 1 secreted from breast cancer cells - A post-translational regulation involving matrix metalloproteinase activity
Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
2009 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 315, no 1, 1-9 p.Article in journal (Refereed) Published
Abstract [en]

Transforming growth factor-beta 1 (TGF-beta 1) promotes cancer progression by regulating tumor cell growth and angiogenesis and high levels of TGF-beta 1 have been associated with metastatic disease and poor prognosis in breast cancer patients. We have previously reported anti-angiogenic effects of the anti-estrogen tamoxifen in breast cancer, by increased matrix metalloproteinase-9 (MMP-9) activity and generation of endostatin. Here, we show that exposure of tamoxifen to ER-positive breast cancer cells for 7 days, decreased extracellular TGF-beta 1. Intracellular TGF-beta 1 levels were unaffected by tamoxifen treatment, indicating a post-translational regulation of TGF-beta 1. Inhibition of MMP activity restored TGF-beta 1 levels, suggesting an involvement of MMP activities in the down-regulation of TGF-beta 1 by tamoxifen. Moreover, using an in vivo model of solid MCF-7 tumors in nude mice, we analyzed tumor levels of TGF-beta 1 after in vivo treatment with estradiol and tamoxifen. Exposure of tumor-bearing mice to tamoxifen significantly decreased tumor TGF-beta 1 protein levels, tumor growth and angiogenesis. In conclusion, our findings suggest a novel mechanism of action of tamoxifen in breast cancer via sex steroid dependent modulation of the proteolytic tumor microenvironment resulting in reduced extracellular TGF-beta 1 levels.

Place, publisher, year, edition, pages
2009. Vol. 315, no 1, 1-9 p.
Keyword [en]
Sex steroids, Breast cancer, TGF-beta l, MMP, Angiogenesis, Nude mice
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-16417DOI: 10.1016/j.yexcr.2008.10.015OAI: oai:DiVA.org:liu-16417DiVA: diva2:139580
Note
Original Publication: Ulrika Nilsson, Jill A Jönsson and Charlotta Dabrosin, Tamoxifen decreases extracellular TGF-beta 1 secreted from breast cancer cells - A post-translational regulation involving matrix metalloproteinase activity, 2009, EXPERIMENTAL CELL RESEARCH, (315), 1, 1-9. http://dx.doi.org/10.1016/j.yexcr.2008.10.015 Copyright: Elsevier Science B.V., Amsterdam http://www.elsevier.com/ Available from: 2009-01-30 Created: 2009-01-23 Last updated: 2017-12-14Bibliographically approved

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Nilsson, UlrikaDabrosin, Charlotta

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