Article (Scientific journals)
Mechanisms governing the accumulation of estrogen receptor alpha in MCF-7 breast cancer cells treated with hydroxytamoxifen and related antiestrogens
Laïos, Ioanna; Journé, Fabrice; Laurent, Guy et al.
2003In Journal of Steroid Biochemistry and Molecular Biology, 87 (2-3), p. 207-221
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Keywords :
[en] Estrogen receptor regulation
Abstract :
[en] This study aimed at a better understanding of estrogen receptor alpha (ER) up regulation induced by partial estrogen antagonists. Effect of treatment with hydroxytamoxifen (OH-Tam) on ER level in MCF-7 cells was investigated by an approach combining ER measurement (enzyme immunoassay) and morphological demonstration (immunofluorescence). Furthermore, the influence of drug exposure on the rates of ER synthesis and degradation was assessed by determining [35S]methionine incorporated into the receptor in different experimental conditions (measurement of synthesis or pulse-chase experiments). ER up regulation was already induced by a 1-h pulse treatment with OH-Tam, thus a continuous exposure was not required. This process appeared reversible (i.e. ER accumulation due to OH-Tam rapidly vanished upon subsequent exposure to 17beta-estradiol (E2) or the pure antiestrogen RU 58668). While OH-Tam did not affect the rate of [35S]methionine incorporation into ER, it clearly caused an impairment of ER degradation (pulse-chase experiments) indicating that up regulation results from a stabilization of the receptor associated with the maintenance of its synthesis. Various tamoxifen derivatives, as well as a few related partial antiestrogens, were compared on the basis of binding ability and propensity to induce ER up regulation. A close relationship was found between both properties. Structure-activity analysis revealed that the capacity of these compounds to induce ER up regulation is associated with characteristics of their aminoalkyle side-chain, similar to those required for antiestrogenicity
Disciplines :
Education & instruction
Author, co-author :
Laïos, Ioanna
Journé, Fabrice
Laurent, Guy 
Nonclercq, Denis ;  Université de Mons > Faculté de Médecine et de Pharmacie > Service d'Histologie
Toillon, Robert-Alain
Seo, H.S.
Leclercq, Guy
Language :
English
Title :
Mechanisms governing the accumulation of estrogen receptor alpha in MCF-7 breast cancer cells treated with hydroxytamoxifen and related antiestrogens
Publication date :
01 November 2003
Journal title :
Journal of Steroid Biochemistry and Molecular Biology
ISSN :
0960-0760
Publisher :
Elsevier, United Kingdom
Volume :
87
Issue :
2-3
Pages :
207-221
Peer reviewed :
Peer Reviewed verified by ORBi
Research unit :
M118 - Histologie
Research institute :
R550 - Institut des Sciences et Technologies de la Santé
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