Tamoxifen decreases extracellular TGF-beta 1 secreted from breast cancer cells - A post-translational regulation involving matrix metalloproteinase activity

Nilsson, Ulrika (författare): Linköpings universitet,Onkologi,Hälsouniversitetet

Jönsson, Jill A. (författare): Linköpings universitet,Onkologi,Hälsouniversitetet

Dabrosin, Charlotta (författare): Östergötlands Läns Landsting,Linköpings universitet,Onkologi,Hälsouniversitetet,Onkologiska kliniken US

(creator_code:org_t)

Elsevier BV, 2009
2009
Engelska.
Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 315:1, s. 1-9

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Abstract Ämnesord

Stäng

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.

Av författaren/redakt...: Nilsson, Ulrika; Jönsson, Jill A.; Dabrosin, Charlo ...

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