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Tamoxifen decreases extracellular TGF-beta 1 secreted from breast cancer cells - A post-translational regulation involving matrix metalloproteinase activity
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
2009 (engelsk)Inngår i: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 315, nr 1, s. 1-9Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
2009. Vol. 315, nr 1, s. 1-9
Emneord [en]
Sex steroids, Breast cancer, TGF-beta l, MMP, Angiogenesis, Nude mice
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URN: urn:nbn:se:liu:diva-16417DOI: 10.1016/j.yexcr.2008.10.015OAI: oai:DiVA.org:liu-16417DiVA, id: diva2:139580
Merknad
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/ Tilgjengelig fra: 2009-01-30 Laget: 2009-01-23 Sist oppdatert: 2017-12-14bibliografisk kontrollert

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