当前位置： SCI文献检索 > CANCER CHEMOTHERAPY AND PHARMACOLOGY期刊下所有文献 > Antagonism of oestrogen action in human breast and endometrial cells in vitro: potential novel antitumour agents.

Antagonism of oestrogen action in human breast and endometrial cells in vitro: potential novel antitumour agents.

Abstract：

PURPOSE:There is a need to find novel oestrogen receptor (ER) ligands that antagonize oestrogen action in the reproductive tissues and would therefore have therapeutic potential in oestrogen-dependent tumours. We tested novel ER ligands in both breast and endometrial cells to profile agonism/antagonism in these oestrogen target reproductive tissues. METHODS:Novel analogues of the ER antagonist ICI 182,780 were synthesized and tested for their ability to inhibit gene expression dependent on oestrogen response elements (ERE) in human breast (MCF-7) and endometrial (Ishikawa) cell lines. This activity was correlated with inhibition of oestrogen-induced cell proliferation and ER binding. RESULTS:The sulphide analogue (compound 1) and sulphone analogue (compound 2) had no intrinsic ERE-dependent agonism in either breast cancer or endometrial cells in culture. All three compounds dose-dependently inhibited ERE-mediated oestrogen agonism. Moreover, these ER ligands inhibited oestrogen-stimulated proliferation of breast cancer and endometrial cells. ICI 182,780, compound 1 and compound 2 were all able to bind both isoforms of the ER (ER alpha and ER beta). In endometrial cells, the relative binding to ER beta correlated with the ERE-dependent antioestrogenic effect of these ligands, suggesting that in this tissue this receptor is the predominant isoform that determines antioestrogenic activity. CONCLUSIONS:The ability of these analogues of ICI 182,780 to inhibit oestrogen-stimulated transcriptional activity and cell proliferation suggests that these agents, in particular the sulphone analogue, have therapeutic potential in the treatment of breast cancer without exhibiting the unwanted oestrogenic effects in the endometrium.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Nuttall ME,Pendrak I,Emery JG,Nadeau DP,Fisher PW,Nicholson TA,Zhu Y,Suva LJ,Kingsbury WD,Gowen M

doi

10.1007/s002800000259

keywords:

subject

Has Abstract

pub_date

2001-05-01 00:00:00

pages

437-43

issue

5

eissn

0344-5704

issn

1432-0843

journal_volume

47

pub_type

杂志文章

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