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Effects of estradio...
Effects of estradiol and tamoxifen on VEGF, soluble VEGFR-1, and VEGFR-2 in breast cancer and endothelial cells
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- Garvin, Stina (author)
- Linköpings universitet,Onkologi,Hälsouniversitetet
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- Nilsson, Ulrika W. (author)
- Linköpings universitet,Onkologi,Hälsouniversitetet
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- Dabrosin, Charlotta (author)
- Linköpings universitet,Onkologi,Hälsouniversitetet
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(creator_code:org_t)
- 2005-10-18
- 2005
- English.
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In: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 93:9, s. 1005-1010
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Abstract
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- Angiogenesis is regulated by the balance between pro- and antiangiogenic factors. Vascular endothelial growth factor (VEGF), acting via the receptors VEGFR-1 and VEGFR-2, is a key mediator of tumour angiogenesis. The soluble form of the VEGF receptor-1 (sVEGFR-1) is an important negative regulator of VEGF-mediated angiogenesis. The majority of breast cancers are oestrogen dependent, but it is not fully understood how oestrogen and the antioestrogen, tamoxifen, affect the balance of angiogenic factors. Angiogenesis is a result of the interplay between cancer and endothelial cells, and sex steroids may exert effects on both cell types. In this study we show that oestradiol decreased secreted sVEGFR-1, increased secreted VEGF, and decreased the ratio of sVEGFR-1/VEGF in MCF-7 human breast cancer cells. The addition of tamoxifen opposed these effects. Moreover, human umbilical vein endothelial cells (HUVEC) incubated with supernatants from oestradiol-treated MCF-7 cells exhibited higher VEGFR-2 levels than controls. In vivo, MCF-7 tumours from oestradiol+tamoxifen-treated nude mice exhibited decreased tumour vasculature. Our results suggest that tamoxifen and oestradiol exert dual effects on the angiogenic environment in breast cancer by regulating cancer cell-secreted angiogenic ligands such as VEGF and sVEGFR-1 and by affecting VEGFR-2 expression of endothelial cells.
Keyword
- breast cancer
- flt-1
- flk-1
- KDR
- MCF-7
- nude mice
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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