In vitro regulation of vascular endothelial growth factor by estrogens and antiestrogens in estrogen-receptor positive breast cancer

被引：47

作者：

Takei H. ^{[1
,2
]}

Lee E.-S. ^{[1
,3
]}

Craig Jordan V. ^{[1
]}

机构：

[1] Northwestern University, Medical School, Robert H. Lurie Comprehensive Cancer Center

[2] Second Department of Surgery, Gunma University, Faculty of Medicine, Maebashi, Gunma 371-8511

[3] Center for Breast Cancer, National Cancer Center

来源：

Breast Cancer | 2002年 / 9卷 / 1期

关键词：

Angiogenesis; Breast cancer; ICI182,780; Tamoxifen; Vascular endothelial growth factor;

D O I：

10.1007/BF02967545

中图分类号：

学科分类号：

摘要：

Background: The effects of antiestrogens on angiogenesis in breast cancer are not fully defined. In this study we investigated the in vitro effects of antiestrogens at different concentrations on vascular endothelial growth factor (VEGF) production in estrogen receptor (ER)-positive breast cancer cells. Method: The dose-dependent effects of 17β-estradiol (E2), 4-hydroxytamoxifen (40HT), and 10182,780 were analyzed both with reference to growth rates and VEGF protein production using enzyme-linked immunosorbent assay (ELISA) in MCF-7 cells. Results: E2 stimulated both the growth rates and VEGF production of MCF-7 cells in the same manner. Although 40HT stimulated the growth rates as an agonistic effect in an estrogen-free media at levels ranging from 1 nM to 1 μM, it did not stimulate VEGF expression at the same levels except for at 1 μM. Although 40HT had a weak agonistic effect on VEGF production at 1 μM in an estrogen-free media, it significantly inhibited Erftimulated VEGF production at the same level. A cytotoxic effect was observed with 10 μM 40HT that paradoxically caused a prominent increase in VEGF production. ICI182,780 had no significant effects on the growth rates or VEGF production in this cell line. Conclusions: These results support the hypothesis that tamoxifen could inhibit angiogenesis induced by estrogens in ER-positive breast cancer cells.

引用

页码：39 / 42

页数：3

共 18 条

[1]

Folkman J., What is the evidence that tumors are angiogenesis dependent?, Journal of the National Cancer Institute, 82, 1, pp. 4-6, (1990)

[2]

Nakamura J., Savinov A., Lu Q., Brodie A., Estrogen regulates vascular endothelial growth/permeability factor expression in 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors, Endocrinology, 137, 12, pp. 5589-5596, (1996)

[3]

Haran E.F., Maretzek A.F., Goldberg I., Horowitz A., Degani H., Tamoxifen enhances cell death in implanted MCF7 breast cancer by inhibiting endothelium growth, Cancer Research, 54, 21, pp. 5511-5514, (1994)

[4]

Evans S.M., Koch C.J., Laughlin K.M., Jenkins W.T., Van Winkle T., Wilson D.F., Tamoxifen induces hypoxia in MCF-7 xenografts, Cancer Research, 57, 22, pp. 5155-5161, (1997)

[5]

Graeber T.G., Osmanian C., Jacks T., Housman D.E., Koch C.J., Lowe S.W., Giaccia A.J., Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours, Nature, 379, 6560, pp. 88-91, (1996)

[6]

Shweiki D., Itin A., Softer D., Et al., Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis, Nature, 359, pp. 843-845, (1992)

[7]

Ruohola J.K., Valve E.M., Karkkainen M.J., Joukov V., Alitalo K., Harkonen P.L., Vascular endothelial growth factors are differentially regulated by steroid hormones and antiestrogens in breast cancer cells, Molecular and Cellular Endocrinology, 149, 1-2, pp. 29-40, (1999)

[8]

Zhang H.T., Craft P., Scott P.A., Et al., Enhancement of tumor growth and vascular density by transfection of vascular endothelial cell growth factor into MCF-7 human breast carcinoma cells, J Natl Cancer Inst, 87, pp. 213-219, (1995)

[9]

Lee E.-S., Horiguchi J., Liu H., Et al., Regulation of angiogenesis in tamoxifen-stimulated breast tumors by the pure antiestrogen ICI 182, 780, Proceedings of AACR, 41, (2000)

[10]

Pink J.J., Jordan V.C., Models of estrogen receptor regulation by estrogens and antiestrogens in breast cancer cell lines, Cancer Research, 56, 10, pp. 2321-2330, (1996)

← 1 2 →