Effect of 17 beta-estradiol, progesterone, synthetic progestins, tibolone, and tibolone metabolites on vascular endothelial growth factor mRNA in breast cancer cells.

Sebastian Mirkin, Benjamin C Wong, David F Archer

The Contraceptive Research and Development Program, The Clinical Research Center, The Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA. mirkins@yahoo.com

Fertility and sterility 2005 Aug

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To determine the effect of 17beta-estradiol, progesterone, medroxyprogesterone acetate, levonorgestrel, norethindrone, tibolone, and tibolone metabolites on vascular endothelial growth factor (VEGF) isoforms 121 and 165 mRNA in two breast cancer cell lines, MCF-7 (estrogen receptor rich) and T47-D (progesterone receptor rich), in vitro. Prospective basic research study. Basic research laboratory. None. MCF-7 and T47-D cells were cultured to 80% confluence in vitro. After 24 hours' incubation in serum-free media, 1.0, 0.1, and 0.01 microM of 17beta-estradiol, tibolone, 3alpha-hydroxytibolone and 3beta-hydroxytibolone were added to MCF-7 cells. Progesterone, medroxyprogesterone acetate, levonorgestrel, norethindrone, and Delta4 tibolone at 1.0, 0.1, and 0.01 microM were added to T47-D cells. The cells plus steroids were incubated for a further 24 hours. Isolation and identification of VEGF isoforms 121 and 165 using semiquantitative polymerase chain reaction, gel electrophoresis, with cyclophilin as an internal control. 17beta-estradiol, tibolone, 3alpha-hydroxytibolone, and 3beta-hydroxytibolone had no effect on VEGF mRNA in MCF-7 cells. Progesterone, medroxyprogesterone acetate, levonorgestrel, and norethindrone increased VEGF mRNA in T47-D cells. Delta4-Tibolone also increased VEGF mRNA but to a lesser extent than the progestogens. 17beta-estradiol, tibolone, and tibolone hydroxy-metabolites had no effect on VEGF mRNA in MCF-7 cells. Progesterone and progestins increased VEGF mRNA in T47-D breast cancer cells, but Delta4-tibolone was less effective than progestogens on this angiogenic gene in the T-47 D cells. This differential effect may be related to breast cancer growth.

Citation

Sebastian Mirkin, Benjamin C Wong, David F Archer. Effect of 17 beta-estradiol, progesterone, synthetic progestins, tibolone, and tibolone metabolites on vascular endothelial growth factor mRNA in breast cancer cells. Fertility and sterility. 2005 Aug;84(2):485-91