Effects of the progestin antagonist RU 486 on T-47D breast cancer cell cycle kinetics and cell cycle regulatory genes.
Possible mechanisms by which the progestin antagonist RU 486 inhibits cell growth were investigated by comparing the effects of the antiprogestin with those of progestin and antiestrogen. Exposure of T-47D breast cancer cells to RU 486 caused a decline in the proportion of cells in S phase, indicative of a block to cell cycle progression in G1 phase. This was accompanied by a marked decrease in c-myc expression but no change in cyclin D1 expression. The cell kinetic data suggest that progestin antagonist inhibition of proliferation and progestin stimulation of proliferation are mediated by opposing effects on the same mechanism. Both estrogen antagonists and progestin antagonists appear to act at a similar part of G1 phase but there are clear differences in their effects on cyclin D1 expression, suggesting that the mechanisms by which these compounds inhibit proliferation are distinct.
Musgrove
E A
EA
Cancer Biology Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, NSW, Australia.
Sutherland
R L
RL
D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D019938:Cyclin D1; D016213:Cyclins / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology*; D015513:Oncogene Proteins / Q000096:biosynthesis; D053284:Polyunsaturated Alkamides; D011282:Pregnenediones / Q000494:pharmacology; D045167:Progesterone Congeners / Q000494:pharmacology; D011372:Progestins / Q000037:antagonists & inhibitors*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D016196:S Phase / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016213:Cyclins; D015513:Oncogene Proteins; D053284:Polyunsaturated Alkamides; D011282:Pregnenediones; D045167:Progesterone Congeners; D011372:Progestins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D019938:Cyclin D1; C020175:16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione; D015735:Mifepristone; D004958:Estradiol; C051781:ICI 164384