The effect of anti-oestrogens on cell growth and progesterone receptor concentration in human endometrial cancer cells (Ishikawa).
The effect of two anti-oestrogens, 4-OH tamoxifen and ICI 164,384, on growth and progesterone receptor (PR) concentration was investigated in the endometrial carcinoma cell line, Ishikawa. Growth stimulation in response to 4-OH tamoxifen was antagonized by ICI 164,384, the latter having no agonist effect when used as a single agent. Similarly, ICI 164,384 antagonized oestradiol-stimulated cell growth. PR was significantly increased following treatment with 4-OH tamoxifen, this response being antagonized in the presence of ICI 164,384. Oestradiol increased PR, although to a lesser extent than did 4-OH tamoxifen; the effect of oestradiol on PR was also antagonized by ICI 164,384. Used as a single agent, ICI 164,384 induced a moderate but statistically significant increase in PR, thus demonstrating partial agonist activity. This agonist property of ICI 164,384 may provide a mechanism of maintaining PR, which is down-regulated during conventional progestin therapy, without undesirable mitogenic activity.
Jamil
A
A
Institute of Obstetrics and Gynaecology, Royal Postgraduate Medical School, Hammersmith Hospital, London.
Croxtall
J D
JD
White
J O
JO
D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists; D005260:Female; D006801:Humans; D053284:Polyunsaturated Alkamides; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism*
D004965:Estrogen Antagonists; D053284:Polyunsaturated Alkamides; D011980:Receptors, Progesterone; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol; C051781:ICI 164384