Effects of two classes of progestagens, pregnane and 19-nortestosterone derivatives, on cell growth of human breast tumor cells: II. T47D cell lines.

Abstract

Two classes of progestagens, e.g. pregnane [Org 2058, progesterone (PROG), R5020, medroxyprogesterone acetate (MPA)] and 19-nortestosterone derived progestagens [norethisterone (NE), levonorgestrel (LNG), 3-ketodesogestrel (KDG), gestodene (GES), Org 30659] were studied for their effect on cell growth of two human breast tumor T47D cell lines of different origin, i.e. from ATCC (A) and Sutherland (S) et al. [Sutherland et al., Cancer Res. 48 (1988) 5084-5091]. The effect of estradiol (E2) and progestagens alone as well as the combined effect of E2 (10(-10) M) and progestagens were investigated at several dose levels. Compared with E2-induced growth at 10(-10) M, pregnane and 19-nortestosterone derived progestagens at 10(-6) M alone did enhance cell growth in T47D-A cells up to 25 and 100% respectively, whereas in T47D-S cells they did not influence growth. All these progestagens at 10(-6) M did not affect E2-induced growth in T47D-A cells, whereas in T47D-S cells they completely reduced cell proliferation at doses between 10(-10) and 10(-8) M. The involvement of progestagen (PR) and estrogen (ER) receptors with respect to growth stimulation was studied by using specific antihormones. In T47D-A cells, the antiprogestagens RU 38486 and Org 31710 could not block progestagen-induced growth. Antiestrogens, like 4-hydroxytamoxifen and ICI 164,384, inhibited the 19-nortestosterone derivative-induced cell growth by approx. 50%. Remarkably, both antiprogestagens alone could also inhibit E2-induced growth in T47D-A cells by about 50%. In T47D-S cells, E2-induced cell growth was completely blocked by both antiprogestagens and antiestrogens. Both antiprogestagens in T47D-S cells were equipotent to 4-hydroxytamoxifen and 10-fold more potent than ICI 164,384. In conclusion pregnane and 19-nortestosterone-derived progestagens stimulated cell growth in T47D-A cells at high unphysiological concentrations, whereas they did not affect cell growth in T47D-S cells. The 19-nortestosterone derivative induced growth in T47D-A cells could partially be inhibited by antiestrogens. In T47D-A cells, E2-induced cell growth was not influenced by both classes of progestagens, whereas in T47D-S cells all tested progestagens, antiprogestagens, and antiestrogens inhibited E2-induced cell growth completely. These results with T47D cells as well as those obtained previously with MCF-7 cells show that subclones of cell lines may respond differently to various types of progestagens in the presence and absence of estrogens.

• Authors: W G Schoonen, J W Joosten, H J Kloosterboer
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 55 Issue 3-4 Pg. 439-44 (Dec 1995) ISSN: 0960-0760 [Print] England
• PMID: 8541241 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Estrenes
• Estrogen Antagonists
• Furans
• Norpregnenes
• Pregnanes
• Pregnenediones
• Org 31710
• Gestodene
• 16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione
• etonogestrel
• Mifepristone
• Progesterone
• Estradiol
• Levonorgestrel
• Nandrolone
• Desogestrel
• Promegestone
• Medroxyprogesterone Acetate
• Norethindrone
• Org 30659

Topics

• Breast Neoplasms (drug therapy, pathology)
• Carcinoma (pathology)
• Cell Division (drug effects)
• Desogestrel (pharmacology)
• Dose-Response Relationship, Drug
• Estradiol (pharmacology)
• Estrenes (pharmacology)
• Estrogen Antagonists (pharmacology)
• Female
• Furans (pharmacology)
• Humans
• Levonorgestrel (pharmacology)
• Medroxyprogesterone Acetate (pharmacology)
• Mifepristone (pharmacology)
• Nandrolone (analogs & derivatives, antagonists & inhibitors, pharmacology)
• Norethindrone (analogs & derivatives, pharmacology)
• Norpregnenes (pharmacology)
• Pregnanes (antagonists & inhibitors, pharmacology)
• Pregnenediones (pharmacology)
• Progesterone (pharmacology)
• Promegestone (pharmacology)
• Tumor Cells, Cultured