Progesterone receptor regulation by retinoic acid in the human breast cancer cell line T-47D.
Data are presented which document the first known effect of retinoic acid on progesterone receptor (PR) gene expression. Treatment of T-47D human breast cancer cells with retinoic acid for 48 h resulted in a marked concentration-dependent decrease in the level of PR mRNA and immunoreactive protein which was similar to the known effect of progestins on these parameters. Retinoic acid, however, did not bind to PR, nor did it cause the previously demonstrated increase in PR molecular weight observed after progestin exposure. When T-47D cells were treated with retinoic acid for 6 h rather than 48 h, no reduction in the level of PR protein was noted at any retinoic acid concentration whereas the effects of retinoic acid on PR mRNA at 6 and 48 h were the same. Examination of the time course of the effects of retinoic acid revealed a rapid decrease in PR mRNA levels detectable 1 h after and maximal 6 h after treatment of T-47D cells with retinoic acid. These effects of retinoic acid contrasted with previously demonstrated progestin effects on PR mRNA which were not apparent until 3 h after and were not maximal until 12 h after treatment. As expected, the PR protein concentration was unaffected for at least 6 h but was maximally decreased 24-48 h after retinoic acid treatment. In summary, retinoic acid treatment of T-47D cells caused a decrease in the cellular PR concentration by decreasing levels of receptor mRNA and protein, suggesting that retinoic acid is capable of modulating sensitivity to progestins in human breast cancer cells.
Clarke
C L
CL
Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, New South Wales, Australia.
Roman
S D
SD
Graham
J
J
Koga
M
M
Sutherland
R L
RL
D015152:Blotting, Northern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D011282:Pregnenediones / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011980:Receptors, Progesterone / Q000502:physiology*; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D011282:Pregnenediones; D012333:RNA, Messenger; D011980:Receptors, Progesterone; C020175:16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione; D014212:Tretinoin