Regulation of progesterone receptor mRNA by oestradiol and antioestrogens in breast cancer cell lines.
The induction of progesterone receptor mRNA by oestradiol and antioestrogens has been characterised in the MCF-7 breast cancer cell line. Progesterone receptor mRNA was induced more than 100-fold by oestradiol. The induction was half-maximal in the presence of 10(-10) M oestradiol and maximum levels were reached after 24 h treatment. Progesterone receptor mRNA was induced to 10% of the oestrogen-induced level by tamoxifen and its metabolite 4'-hydroxytamoxifen. The increase was half-maximal in the presence of 5 X 10(-8) M tamoxifen or 5 X 10(-10) M 4'-hydroxytamoxifen. In contrast, neither the benzothiophene antioestrogen LY117018 nor the 7 alpha-alkyl steroidal antioestrogen ICI 164,384 had any effect on progesterone receptor mRNA. The progesterone receptor mRNA was also induced by oestrogen in a T47D subline and in two other oestrogen-responsive breast cancer cell lines (ZR-75, EFM-19). Tamoxifen was a partial oestrogen for progesterone receptor mRNA induction in each of these cell lines. The large induction of the progesterone receptor mRNA by oestrogen in all 4 breast cancer cell lines supports the contention that the progesterone receptor may be a good predictive marker of hormonal response in human breast cancer.
May
F E
FE
University Department of Pathology, Royal Victoria Infirmary, Newcastle upon Tyne, U.K.
Johnson
M D
MD
Wiseman
L R
LR
Wakeling
A E
AE
Kastner
P
P
Westley
B R
BR
D000818:Animals; D001345:Autoradiography; D015152:Blotting, Northern; D004591:Electrophoresis, Polyacrylamide Gel; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000503:physiopathology; D053284:Polyunsaturated Alkamides; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000502:physiology*; D011980:Receptors, Progesterone / Q000187:drug effects / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D053284:Polyunsaturated Alkamides; D011759:Pyrrolidines; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D013876:Thiophenes; D013629:Tamoxifen; D004958:Estradiol; C025430:LY 117018; C051781:ICI 164384