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

Gabriella Ferrandina, Franco Oreste Ranelletti, Giovanni Scambia, Pierluigi Benedetti Panici, Giuseppe D'Agostino, Mauro Piantelli, Giulio Isola, Salvatore Mancuso

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)123-131
Number of pages9
JournalCancer Letters
Volume96
Issue number1
DOIs
Publication statusPublished - Sep 4 1995

Fingerprint

Tamoxifen
Ovarian Neoplasms
Ligands
type II estrogen binding site
Cytosol
Estradiol
Cell Line

Keywords

  • Antiproliferative activity
  • Tamoxifen
  • Type II estrogen binding sites

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Biology

Cite this

Ferrandina, G., Ranelletti, F. O., Scambia, G., Panici, P. B., D'Agostino, G., Piantelli, M., ... Mancuso, S. (1995). Interaction of tamoxifen with cytosolic and nuclear Type II estrogen binding sites (Type II EBS). Cancer Letters, 96(1), 123-131. https://doi.org/10.1016/0304-3835(95)03922-J

Interaction of tamoxifen with cytosolic and nuclear Type II estrogen binding sites (Type II EBS). / Ferrandina, Gabriella; Ranelletti, Franco Oreste; Scambia, Giovanni; Panici, Pierluigi Benedetti; D'Agostino, Giuseppe; Piantelli, Mauro; Isola, Giulio; Mancuso, Salvatore.

In: Cancer Letters, Vol. 96, No. 1, 04.09.1995, p. 123-131.

Research output: Contribution to journalArticle

Ferrandina, G, Ranelletti, FO, Scambia, G, Panici, PB, D'Agostino, G, Piantelli, M, Isola, G & Mancuso, S 1995, 'Interaction of tamoxifen with cytosolic and nuclear Type II estrogen binding sites (Type II EBS)', Cancer Letters, vol. 96, no. 1, pp. 123-131. https://doi.org/10.1016/0304-3835(95)03922-J
Ferrandina, Gabriella ; Ranelletti, Franco Oreste ; Scambia, Giovanni ; Panici, Pierluigi Benedetti ; D'Agostino, Giuseppe ; Piantelli, Mauro ; Isola, Giulio ; Mancuso, Salvatore. / Interaction of tamoxifen with cytosolic and nuclear Type II estrogen binding sites (Type II EBS). In: Cancer Letters. 1995 ; Vol. 96, No. 1. pp. 123-131.
@article{e6f09eb1954a4b10a7ce91ba7a47d388,
title = "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.",
keywords = "Antiproliferative activity, Tamoxifen, Type II estrogen binding sites",
author = "Gabriella Ferrandina and Ranelletti, {Franco Oreste} and Giovanni Scambia and Panici, {Pierluigi Benedetti} and Giuseppe D'Agostino and Mauro Piantelli and Giulio Isola and Salvatore Mancuso",
year = "1995",
month = "9",
day = "4",
doi = "10.1016/0304-3835(95)03922-J",
language = "English",
volume = "96",
pages = "123--131",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Interaction of tamoxifen with cytosolic and nuclear Type II estrogen binding sites (Type II EBS)

AU - Ferrandina, Gabriella

AU - Ranelletti, Franco Oreste

AU - Scambia, Giovanni

AU - Panici, Pierluigi Benedetti

AU - D'Agostino, Giuseppe

AU - Piantelli, Mauro

AU - Isola, Giulio

AU - Mancuso, Salvatore

PY - 1995/9/4

Y1 - 1995/9/4

N2 - 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.

AB - 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.

KW - Antiproliferative activity

KW - Tamoxifen

KW - Type II estrogen binding sites

UR - http://www.scopus.com/inward/record.url?scp=0029121606&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029121606&partnerID=8YFLogxK

U2 - 10.1016/0304-3835(95)03922-J

DO - 10.1016/0304-3835(95)03922-J

M3 - Article

C2 - 7553600

AN - SCOPUS:0029121606

VL - 96

SP - 123

EP - 131

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

IS - 1

ER -