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


METHODS
Prospective basic research study.


METHODS
Basic research laboratory.


METHODS
None.


METHODS
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.


METHODS
Isolation and identification of VEGF isoforms 121 and 165 using semiquantitative polymerase chain reaction, gel electrophoresis, with cyclophilin as an internal control.


RESULTS
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.


CONCLUSIONS
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.
Mirkin
Sebastian
S
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
Wong
Benjamin C
BC
Archer
David F
DF
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009652:Norpregnenes / Q000378:metabolism* / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000494:pharmacology*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
D009652:Norpregnenes; D045167:Progesterone Congeners; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D011374:Progesterone; D004958:Estradiol; C027385:tibolone