Tamoxifen aziridine binding to cytosolic proteins from human breast cancer is negatively associated to estrogen receptors, progesterone receptors, pS2 and cathepsin-D.

[3H]Tamoxifen Aziridine ([3H]TAZ) is a derivative of the antiestrogen tamoxifen that covalently labels the Estrogen Receptor (ER), and perhaps other uncharacterized proteins. In a previous article we described that [3H]TAZ binds to a cytosolic protein from human uterine tissues that shares some, but...

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Autores: Morales González, Manuel José, Navarro, Domingo, Doreste, Hilario, Cabrera, Juan J., Díaz-Chico, Juan C., Díaz-Chico, Bonifacio N.
Tipo de recurso: artículo
Fecha de publicación:1998
País:España
Institución:Universidad de La Laguna (ULL)
Repositorio:RIULL. Repositorio Institucional de la Universidad de La Laguna
OAI Identifier:oai:riull.ull.es:915/40049
Acceso en línea:http://riull.ull.es/xmlui/handle/915/40049
Access Level:acceso abierto
Palabra clave:Breast cancer
Estrogen receptors
Progesterone receptor
pS2
Cathepsin-D
Native receptor
Tamoxifen aziridine
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spelling Tamoxifen aziridine binding to cytosolic proteins from human breast cancer is negatively associated to estrogen receptors, progesterone receptors, pS2 and cathepsin-D.Morales González, Manuel JoséNavarro, DomingoDoreste, HilarioCabrera, Juan J.Díaz-Chico, Juan C.Díaz-Chico, Bonifacio N.Breast cancerEstrogen receptorsProgesterone receptorpS2Cathepsin-DNative receptorTamoxifen aziridine[3H]Tamoxifen Aziridine ([3H]TAZ) is a derivative of the antiestrogen tamoxifen that covalently labels the Estrogen Receptor (ER), and perhaps other uncharacterized proteins. In a previous article we described that [3H]TAZ binds to a cytosolic protein from human uterine tissues that shares some, but not all, the ER properties. Here we have extended these studies to [3H]TAZ binding to cytosol proteins from human breast cancer specimens, and studied its quantitative association with other molecular markers and clinico-pathological variables. Cytosols were obtained in hypotonic buffer containing 20 mM molybdate and protease inhibitors, incubated with [3H]TAZ, and subjected to Sucrose Gradient Analysis (SGA). A [3H]TAZ labeled peak that consistently migrated with the 4S fractions was found in most of the assayed cytosols (range of 0 to 1278 fmol/mg p.). The 4S peak of [3H]TAZ was partially inhibited by both estrogens and antiestrogens. When [3H]E2 was used instead of [3H]TAZ, only an 8S peak was detected. [3H]TAZ was covalently bound to a protein with an apparent MW of 65 kDa, as determined by SDS-PAGE and fluorography. The mean of [3H]TAZ binding was significantly higher in the subgroups of samples classified as ER-, PR-, pS2- or cathepsin D-, than in the respective positive subgroups (P < 0.01 in all the cases). [3H]TAZ binding was not associated with clinico-pathological variables, except that its mean was significantly larger in tumors larger than 5 cm than in smaller tumors. These results, and those previously reported, suggest that: 1) [3H]TAZ labels a cytosolic protein present in human breast cancers and uterine tissues that does not share all the ER properties, and 2) the [3H]TAZ binding by breast cancer cytosols is negatively associated with markers of estrogenic dependency, and its quantification may provide valuable information on antiestrogen responsiveness of a given tumor.Medicina Interna, Dermatología y Psiquiatría202420241998info:eu-repo/semantics/articleapplication/pdfhttp://riull.ull.es/xmlui/handle/915/40049reponame:RIULL. Repositorio Institucional de la Universidad de La Lagunainstname:Universidad de La Laguna (ULL)InglésBreast Cancer Research and Treatment, v.50 n.2, 1998Licencia Creative Commons (Reconocimiento-No comercial-Sin obras derivadas 4.0 Internacional)info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es_ESoai:riull.ull.es:915/400492026-06-22T13:13:57Z
dc.title.none.fl_str_mv Tamoxifen aziridine binding to cytosolic proteins from human breast cancer is negatively associated to estrogen receptors, progesterone receptors, pS2 and cathepsin-D.
title Tamoxifen aziridine binding to cytosolic proteins from human breast cancer is negatively associated to estrogen receptors, progesterone receptors, pS2 and cathepsin-D.
spellingShingle Tamoxifen aziridine binding to cytosolic proteins from human breast cancer is negatively associated to estrogen receptors, progesterone receptors, pS2 and cathepsin-D.
Morales González, Manuel José
Breast cancer
Estrogen receptors
Progesterone receptor
pS2
Cathepsin-D
Native receptor
Tamoxifen aziridine
title_short Tamoxifen aziridine binding to cytosolic proteins from human breast cancer is negatively associated to estrogen receptors, progesterone receptors, pS2 and cathepsin-D.
title_full Tamoxifen aziridine binding to cytosolic proteins from human breast cancer is negatively associated to estrogen receptors, progesterone receptors, pS2 and cathepsin-D.
title_fullStr Tamoxifen aziridine binding to cytosolic proteins from human breast cancer is negatively associated to estrogen receptors, progesterone receptors, pS2 and cathepsin-D.
title_full_unstemmed Tamoxifen aziridine binding to cytosolic proteins from human breast cancer is negatively associated to estrogen receptors, progesterone receptors, pS2 and cathepsin-D.
title_sort Tamoxifen aziridine binding to cytosolic proteins from human breast cancer is negatively associated to estrogen receptors, progesterone receptors, pS2 and cathepsin-D.
dc.creator.none.fl_str_mv Morales González, Manuel José
Navarro, Domingo
Doreste, Hilario
Cabrera, Juan J.
Díaz-Chico, Juan C.
Díaz-Chico, Bonifacio N.
author Morales González, Manuel José
author_facet Morales González, Manuel José
Navarro, Domingo
Doreste, Hilario
Cabrera, Juan J.
Díaz-Chico, Juan C.
Díaz-Chico, Bonifacio N.
author_role author
author2 Navarro, Domingo
Doreste, Hilario
Cabrera, Juan J.
Díaz-Chico, Juan C.
Díaz-Chico, Bonifacio N.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Medicina Interna, Dermatología y Psiquiatría
dc.subject.none.fl_str_mv Breast cancer
Estrogen receptors
Progesterone receptor
pS2
Cathepsin-D
Native receptor
Tamoxifen aziridine
topic Breast cancer
Estrogen receptors
Progesterone receptor
pS2
Cathepsin-D
Native receptor
Tamoxifen aziridine
description [3H]Tamoxifen Aziridine ([3H]TAZ) is a derivative of the antiestrogen tamoxifen that covalently labels the Estrogen Receptor (ER), and perhaps other uncharacterized proteins. In a previous article we described that [3H]TAZ binds to a cytosolic protein from human uterine tissues that shares some, but not all, the ER properties. Here we have extended these studies to [3H]TAZ binding to cytosol proteins from human breast cancer specimens, and studied its quantitative association with other molecular markers and clinico-pathological variables. Cytosols were obtained in hypotonic buffer containing 20 mM molybdate and protease inhibitors, incubated with [3H]TAZ, and subjected to Sucrose Gradient Analysis (SGA). A [3H]TAZ labeled peak that consistently migrated with the 4S fractions was found in most of the assayed cytosols (range of 0 to 1278 fmol/mg p.). The 4S peak of [3H]TAZ was partially inhibited by both estrogens and antiestrogens. When [3H]E2 was used instead of [3H]TAZ, only an 8S peak was detected. [3H]TAZ was covalently bound to a protein with an apparent MW of 65 kDa, as determined by SDS-PAGE and fluorography. The mean of [3H]TAZ binding was significantly higher in the subgroups of samples classified as ER-, PR-, pS2- or cathepsin D-, than in the respective positive subgroups (P < 0.01 in all the cases). [3H]TAZ binding was not associated with clinico-pathological variables, except that its mean was significantly larger in tumors larger than 5 cm than in smaller tumors. These results, and those previously reported, suggest that: 1) [3H]TAZ labels a cytosolic protein present in human breast cancers and uterine tissues that does not share all the ER properties, and 2) the [3H]TAZ binding by breast cancer cytosols is negatively associated with markers of estrogenic dependency, and its quantification may provide valuable information on antiestrogen responsiveness of a given tumor.
publishDate 1998
dc.date.none.fl_str_mv 1998
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://riull.ull.es/xmlui/handle/915/40049
url http://riull.ull.es/xmlui/handle/915/40049
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Breast Cancer Research and Treatment, v.50 n.2, 1998
dc.rights.none.fl_str_mv Licencia Creative Commons (Reconocimiento-No comercial-Sin obras derivadas 4.0 Internacional)
info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es_ES
rights_invalid_str_mv Licencia Creative Commons (Reconocimiento-No comercial-Sin obras derivadas 4.0 Internacional)
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es_ES
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:RIULL. Repositorio Institucional de la Universidad de La Laguna
instname:Universidad de La Laguna (ULL)
instname_str Universidad de La Laguna (ULL)
reponame_str RIULL. Repositorio Institucional de la Universidad de La Laguna
collection RIULL. Repositorio Institucional de la Universidad de La Laguna
repository.name.fl_str_mv
repository.mail.fl_str_mv
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