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Interaction of tamoxifen with cytosolic and nuclear type II estrogen binding sites (type II EBS).

Abstract：

:The aim of this study was to investigate the interaction of tamoxifen (TAM) with the so-called Type II estrogen binding sites (Type II EBS) in both the cytosolic and the nuclear fraction of the ER-negative A 2780 human ovarian cancer cell line and in an ER-negative ovarian cancer tissue. Although cytosolic and nuclear Type II EBS in A 2780 cells showed substantially similar binding characteristics in terms of ligand affinity and specificity, TAM, while exhibiting the ability to displace [3H]estradiol from cytosolic Type II EBS failed to interact with nuclear Type II EBS. The ability of TAM to interact only with cytosolic Type II EBS seems also to be a characteristic of ovarian cancer tissue and to be shared by several TAM metabolites. The hypothesis that the interaction of TAM with cytosolic Type II EBS could mobilize the true endogenous ligand of Type II EBS which would become available for binding to nuclear Type II EBS was tested by incubating the nuclear fraction with the cytosolic fraction. In the presence of cytosol, TAM acquires the ability to displace the tracer from nuclear Type II EBS but when the cytosolic fraction was DCC, stripped in order to remove the endogenous ligand, the competing activity of TAM for nuclear Type II EBS was abolished. Our results suggest that TAM does not interact with nuclear Type II EBS, but can favor the nuclear binding of endogenous ligand by displacing it from cytosolic Type II EBS.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Ferrandina G,Ranelletti FO,Scambia G,Benedetti Panici P,D'Agostino G,Piantelli M,Isola G,Mancuso S

doi

10.1016/0304-3835(95)03922-j

subject

Has Abstract

pub_date

1995-09-04 00:00:00

pages

123-31

issue

1

eissn

0304-3835

issn

1872-7980

pii

030438359503922J

journal_volume

96

pub_type

杂志文章

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