Progesterone receptor expression in medroxyprogesterone acetate-induced murine mammary carcinomas and response to endocrine treatment

Autores
Helguero, Luisa A.; Viegas, Marcelo; Asaithamby, Aroumougame; Shyamala, Gopalan; Lanari, Claudia Lee Malvina; Molinolo, Alfredo
Año de publicación
2003
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Using medroxyprogesterone acetate (MPA) as a carcinogen, we were able to induce in BALB/c female mice, several progestin-dependent mammary ductal carcinomas that regress completely with estrogen or antiprogestins and are maintained by serial transplantations in syngeneic mice. Progestin-independent variants were subsequently generated or appeared spontaneously. Based on their response to estrogen or antiprogestins, we subdivided them into responsive progestin-independent (R-PI) variants which regress completely and unresponsive progestin-independent (UR-PI) carcinomas which are resistant to both families of compounds. In this study we have investigated progesterone receptor (PR) expression in six responsive progestin-dependent, six R-PI, and three UR-PI tumors. Progestin-dependent and R-PI tumors disclosed a higher expression of the PR(A) isoform as compared with PR(B), as well as an additional band of 78 kDa that was not detected in uterine tissue; all were down-regulated by progestins. UR-PI tumors expressed lower levels of all bands in western blots, but were highly reactive by immunohistochemistry. PR RNA expression was detected in both, UR-PI and R-PI tumors. PR binding was comparable in progestin-dependent and R-PI tumors. In the three UR-PI tumors, only 29/61 (48%) of the samples evaluated showed low binding levels, the rest were negative. This report is the first to describe in an experimental model of breast cancer the expression of PR isoforms and their distribution. Our results suggest the expression of functionally altered isoforms in a subgroup of mammary carcinomas, which may explain their lack of hormone response.
Fil: Helguero, Luisa A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Viegas, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Asaithamby, Aroumougame. University of California at Berkeley; Estados Unidos
Fil: Shyamala, Gopalan. University of California at Berkeley; Estados Unidos
Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Molinolo, Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
Carcinoma
Mammary Neoplasm
Breast Cancer
Medroxyprogesterone Acetate
Progesterone Congeners
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/36232
Acceder
id CONICETDig_ae30aabbec58ddb597a4f84738e5a953
oai_identifier_str oai:ri.conicet.gov.ar:11336/36232
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Progesterone receptor expression in medroxyprogesterone acetate-induced murine mammary carcinomas and response to endocrine treatmentHelguero, Luisa A.Viegas, MarceloAsaithamby, AroumougameShyamala, GopalanLanari, Claudia Lee MalvinaMolinolo, AlfredoCarcinomaMammary NeoplasmBreast CancerMedroxyprogesterone AcetateProgesterone Congenershttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Using medroxyprogesterone acetate (MPA) as a carcinogen, we were able to induce in BALB/c female mice, several progestin-dependent mammary ductal carcinomas that regress completely with estrogen or antiprogestins and are maintained by serial transplantations in syngeneic mice. Progestin-independent variants were subsequently generated or appeared spontaneously. Based on their response to estrogen or antiprogestins, we subdivided them into responsive progestin-independent (R-PI) variants which regress completely and unresponsive progestin-independent (UR-PI) carcinomas which are resistant to both families of compounds. In this study we have investigated progesterone receptor (PR) expression in six responsive progestin-dependent, six R-PI, and three UR-PI tumors. Progestin-dependent and R-PI tumors disclosed a higher expression of the PR(A) isoform as compared with PR(B), as well as an additional band of 78 kDa that was not detected in uterine tissue; all were down-regulated by progestins. UR-PI tumors expressed lower levels of all bands in western blots, but were highly reactive by immunohistochemistry. PR RNA expression was detected in both, UR-PI and R-PI tumors. PR binding was comparable in progestin-dependent and R-PI tumors. In the three UR-PI tumors, only 29/61 (48%) of the samples evaluated showed low binding levels, the rest were negative. This report is the first to describe in an experimental model of breast cancer the expression of PR isoforms and their distribution. Our results suggest the expression of functionally altered isoforms in a subgroup of mammary carcinomas, which may explain their lack of hormone response.Fil: Helguero, Luisa A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Viegas, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Asaithamby, Aroumougame. University of California at Berkeley; Estados UnidosFil: Shyamala, Gopalan. University of California at Berkeley; Estados UnidosFil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Molinolo, Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaKluwer Academic/plenum Publ2003-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/36232Helguero, Luisa A.; Viegas, Marcelo; Asaithamby, Aroumougame; Shyamala, Gopalan; Lanari, Claudia Lee Malvina; et al.; Progesterone receptor expression in medroxyprogesterone acetate-induced murine mammary carcinomas and response to endocrine treatment; Kluwer Academic/plenum Publ; Breast Cancer Research and Treatment; 79; 3; 12-2003; 379-3900167-68061573-7217CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1023/A:1024029826248info:eu-repo/semantics/altIdentifier/pmid/12846422info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:04:54Zoai:ri.conicet.gov.ar:11336/36232instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:04:54.741CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Progesterone receptor expression in medroxyprogesterone acetate-induced murine mammary carcinomas and response to endocrine treatment
title Progesterone receptor expression in medroxyprogesterone acetate-induced murine mammary carcinomas and response to endocrine treatment
spellingShingle Progesterone receptor expression in medroxyprogesterone acetate-induced murine mammary carcinomas and response to endocrine treatment
Helguero, Luisa A.
Carcinoma
Mammary Neoplasm
Breast Cancer
Medroxyprogesterone Acetate
Progesterone Congeners
title_short Progesterone receptor expression in medroxyprogesterone acetate-induced murine mammary carcinomas and response to endocrine treatment
title_full Progesterone receptor expression in medroxyprogesterone acetate-induced murine mammary carcinomas and response to endocrine treatment
title_fullStr Progesterone receptor expression in medroxyprogesterone acetate-induced murine mammary carcinomas and response to endocrine treatment
title_full_unstemmed Progesterone receptor expression in medroxyprogesterone acetate-induced murine mammary carcinomas and response to endocrine treatment
title_sort Progesterone receptor expression in medroxyprogesterone acetate-induced murine mammary carcinomas and response to endocrine treatment
dc.creator.none.fl_str_mv Helguero, Luisa A.
Viegas, Marcelo
Asaithamby, Aroumougame
Shyamala, Gopalan
Lanari, Claudia Lee Malvina
Molinolo, Alfredo
author Helguero, Luisa A.
author_facet Helguero, Luisa A.
Viegas, Marcelo
Asaithamby, Aroumougame
Shyamala, Gopalan
Lanari, Claudia Lee Malvina
Molinolo, Alfredo
author_role author
author2 Viegas, Marcelo
Asaithamby, Aroumougame
Shyamala, Gopalan
Lanari, Claudia Lee Malvina
Molinolo, Alfredo
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Carcinoma
Mammary Neoplasm
Breast Cancer
Medroxyprogesterone Acetate
Progesterone Congeners
topic Carcinoma
Mammary Neoplasm
Breast Cancer
Medroxyprogesterone Acetate
Progesterone Congeners
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Using medroxyprogesterone acetate (MPA) as a carcinogen, we were able to induce in BALB/c female mice, several progestin-dependent mammary ductal carcinomas that regress completely with estrogen or antiprogestins and are maintained by serial transplantations in syngeneic mice. Progestin-independent variants were subsequently generated or appeared spontaneously. Based on their response to estrogen or antiprogestins, we subdivided them into responsive progestin-independent (R-PI) variants which regress completely and unresponsive progestin-independent (UR-PI) carcinomas which are resistant to both families of compounds. In this study we have investigated progesterone receptor (PR) expression in six responsive progestin-dependent, six R-PI, and three UR-PI tumors. Progestin-dependent and R-PI tumors disclosed a higher expression of the PR(A) isoform as compared with PR(B), as well as an additional band of 78 kDa that was not detected in uterine tissue; all were down-regulated by progestins. UR-PI tumors expressed lower levels of all bands in western blots, but were highly reactive by immunohistochemistry. PR RNA expression was detected in both, UR-PI and R-PI tumors. PR binding was comparable in progestin-dependent and R-PI tumors. In the three UR-PI tumors, only 29/61 (48%) of the samples evaluated showed low binding levels, the rest were negative. This report is the first to describe in an experimental model of breast cancer the expression of PR isoforms and their distribution. Our results suggest the expression of functionally altered isoforms in a subgroup of mammary carcinomas, which may explain their lack of hormone response.
Fil: Helguero, Luisa A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Viegas, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Asaithamby, Aroumougame. University of California at Berkeley; Estados Unidos
Fil: Shyamala, Gopalan. University of California at Berkeley; Estados Unidos
Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Molinolo, Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description Using medroxyprogesterone acetate (MPA) as a carcinogen, we were able to induce in BALB/c female mice, several progestin-dependent mammary ductal carcinomas that regress completely with estrogen or antiprogestins and are maintained by serial transplantations in syngeneic mice. Progestin-independent variants were subsequently generated or appeared spontaneously. Based on their response to estrogen or antiprogestins, we subdivided them into responsive progestin-independent (R-PI) variants which regress completely and unresponsive progestin-independent (UR-PI) carcinomas which are resistant to both families of compounds. In this study we have investigated progesterone receptor (PR) expression in six responsive progestin-dependent, six R-PI, and three UR-PI tumors. Progestin-dependent and R-PI tumors disclosed a higher expression of the PR(A) isoform as compared with PR(B), as well as an additional band of 78 kDa that was not detected in uterine tissue; all were down-regulated by progestins. UR-PI tumors expressed lower levels of all bands in western blots, but were highly reactive by immunohistochemistry. PR RNA expression was detected in both, UR-PI and R-PI tumors. PR binding was comparable in progestin-dependent and R-PI tumors. In the three UR-PI tumors, only 29/61 (48%) of the samples evaluated showed low binding levels, the rest were negative. This report is the first to describe in an experimental model of breast cancer the expression of PR isoforms and their distribution. Our results suggest the expression of functionally altered isoforms in a subgroup of mammary carcinomas, which may explain their lack of hormone response.
publishDate 2003
dc.date.none.fl_str_mv 2003-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/36232
Helguero, Luisa A.; Viegas, Marcelo; Asaithamby, Aroumougame; Shyamala, Gopalan; Lanari, Claudia Lee Malvina; et al.; Progesterone receptor expression in medroxyprogesterone acetate-induced murine mammary carcinomas and response to endocrine treatment; Kluwer Academic/plenum Publ; Breast Cancer Research and Treatment; 79; 3; 12-2003; 379-390
0167-6806
1573-7217
CONICET Digital
CONICET
url http://hdl.handle.net/11336/36232
identifier_str_mv Helguero, Luisa A.; Viegas, Marcelo; Asaithamby, Aroumougame; Shyamala, Gopalan; Lanari, Claudia Lee Malvina; et al.; Progesterone receptor expression in medroxyprogesterone acetate-induced murine mammary carcinomas and response to endocrine treatment; Kluwer Academic/plenum Publ; Breast Cancer Research and Treatment; 79; 3; 12-2003; 379-390
0167-6806
1573-7217
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1023/A:1024029826248
info:eu-repo/semantics/altIdentifier/pmid/12846422
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Kluwer Academic/plenum Publ
publisher.none.fl_str_mv Kluwer Academic/plenum Publ
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.986718

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