p21,p27 and p53 in estrogen and antiprogestin- induced regression of experimental mouse mammary ductal carcinomas

Autores
Vanzulli, Silvia; Efeyan, Alejo; Benavides, Fernando; Helguero, Luisa A.; Peters, Giselle; Shen, Jianjun; Conti, Claudio J.; Lanari, Claudia Lee Malvina; Molinolo, Alfredo
Año de publicación
2002
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Metastatic mammary carcinoma tumor lines 59-2-HI and C7-2-HI originated in female BALB/c mice treated with medroxyprogesterone acetate and are maintained by syngeneic transplantation. Both lines express estrogen (ER) and progesterone receptors (PR) and regress completely after estradiol (E 2 ) or antiprogestin treatment. The BET tumor line, of similar origin and biological features, regresses only after E 2 treatment. To investigate possible differences between E 2 - and antiprogestin-mediated effects we evaluated the morphological features, mitosis and apoptosis, and the differential expression of cell-cycle inhibitors associated with tumor regression. Treatments started when tumors reached 50–100 mm 2 . After 24–96 h, tumors were excised and processed for morphological and immunohistochemical studies. Regression was associated with a significant and early decrease in the number of mitosis and with higher percentages of apoptotic cells. These phenomena were accompanied by an increase in p21 and p27 expression in the E 2 and antiprogestin-responsive lines treated with E 2 , RU 38.486 or ZK 98.299 ( P < 0.05). In BET tumors treated with E 2 , p21 expression remained within basal levels and only p27 increased ( P < 0.05). p53 was low in control 59-2-HI and C7-2-HI tumors and increased after treatment ( P < 0.05) whereas BET untreated tumors already expressed high levels of p53 and MDM2. Although the immunohistochemical findings were compatible with alterations of p53, SSCP evaluation failed to disclose the presence of mutations, suggesting that the defective expression of p21 is related to an impaired p53 pathway. UV irradiation failed to increase p21 expression in BET, but was able to induce p53 and p21 in 59-2-HI and C7-2-HI tumors. The absence of an increased expression of p21 in E 2 -regressing BET lesions suggests that this protein is not necessary for estrogen-induced regression, but may be essential for antiprogestin action. Our results also suggest that p53/MDM2 alterations may be one of the mechanisms responsible for selected hormone resistance in breast carcinomas.
Fil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Efeyan, Alejo. 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: Benavides, Fernando. University of Texas; Estados Unidos
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: Peters, Giselle. 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: Shen, Jianjun. University of Texas; Estados Unidos
Fil: Conti, Claudio J.. University of Texas; 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
Apoptosis
Mammary Neoplasm
Tumor Supressor
Proto-Oncogene Proteins P21
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:11336/31324
Acceder
id CONICETDig_2b77b645c186b83a41bd0ea61a27f707
oai_identifier_str oai:ri.conicet.gov.ar:11336/31324
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling p21,p27 and p53 in estrogen and antiprogestin- induced regression of experimental mouse mammary ductal carcinomasVanzulli, SilviaEfeyan, AlejoBenavides, FernandoHelguero, Luisa A.Peters, GiselleShen, JianjunConti, Claudio J.Lanari, Claudia Lee MalvinaMolinolo, AlfredoApoptosisMammary NeoplasmTumor SupressorProto-Oncogene Proteins P21https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Metastatic mammary carcinoma tumor lines 59-2-HI and C7-2-HI originated in female BALB/c mice treated with medroxyprogesterone acetate and are maintained by syngeneic transplantation. Both lines express estrogen (ER) and progesterone receptors (PR) and regress completely after estradiol (E 2 ) or antiprogestin treatment. The BET tumor line, of similar origin and biological features, regresses only after E 2 treatment. To investigate possible differences between E 2 - and antiprogestin-mediated effects we evaluated the morphological features, mitosis and apoptosis, and the differential expression of cell-cycle inhibitors associated with tumor regression. Treatments started when tumors reached 50–100 mm 2 . After 24–96 h, tumors were excised and processed for morphological and immunohistochemical studies. Regression was associated with a significant and early decrease in the number of mitosis and with higher percentages of apoptotic cells. These phenomena were accompanied by an increase in p21 and p27 expression in the E 2 and antiprogestin-responsive lines treated with E 2 , RU 38.486 or ZK 98.299 ( P < 0.05). In BET tumors treated with E 2 , p21 expression remained within basal levels and only p27 increased ( P < 0.05). p53 was low in control 59-2-HI and C7-2-HI tumors and increased after treatment ( P < 0.05) whereas BET untreated tumors already expressed high levels of p53 and MDM2. Although the immunohistochemical findings were compatible with alterations of p53, SSCP evaluation failed to disclose the presence of mutations, suggesting that the defective expression of p21 is related to an impaired p53 pathway. UV irradiation failed to increase p21 expression in BET, but was able to induce p53 and p21 in 59-2-HI and C7-2-HI tumors. The absence of an increased expression of p21 in E 2 -regressing BET lesions suggests that this protein is not necessary for estrogen-induced regression, but may be essential for antiprogestin action. Our results also suggest that p53/MDM2 alterations may be one of the mechanisms responsible for selected hormone resistance in breast carcinomas.Fil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Efeyan, Alejo. 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: Benavides, Fernando. University of Texas; Estados UnidosFil: 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: Peters, Giselle. 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: Shen, Jianjun. University of Texas; Estados UnidosFil: Conti, Claudio J.. University of Texas; 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; ArgentinaOxford University Press2002-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/31324Molinolo, Alfredo; Lanari, Claudia Lee Malvina; Conti, Claudio J.; Shen, Jianjun; Peters, Giselle; Helguero, Luisa A.; et al.; p21,p27 and p53 in estrogen and antiprogestin- induced regression of experimental mouse mammary ductal carcinomas; Oxford University Press; Carcinogenesis; 23; 5; 12-2002; 749-7570143-33341460-2180CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/carcin/article/23/5/749/2608222info:eu-repo/semantics/altIdentifier/doi/10.1093/carcin/23.5.749info:eu-repo/semantics/altIdentifier/pmid/https://www.ncbi.nlm.nih.gov/pubmed/12016147info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:07:12Zoai:ri.conicet.gov.ar:11336/31324instacron: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 10:07:12.769CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv p21,p27 and p53 in estrogen and antiprogestin- induced regression of experimental mouse mammary ductal carcinomas
title p21,p27 and p53 in estrogen and antiprogestin- induced regression of experimental mouse mammary ductal carcinomas
spellingShingle p21,p27 and p53 in estrogen and antiprogestin- induced regression of experimental mouse mammary ductal carcinomas
Vanzulli, Silvia
Apoptosis
Mammary Neoplasm
Tumor Supressor
Proto-Oncogene Proteins P21
title_short p21,p27 and p53 in estrogen and antiprogestin- induced regression of experimental mouse mammary ductal carcinomas
title_full p21,p27 and p53 in estrogen and antiprogestin- induced regression of experimental mouse mammary ductal carcinomas
title_fullStr p21,p27 and p53 in estrogen and antiprogestin- induced regression of experimental mouse mammary ductal carcinomas
title_full_unstemmed p21,p27 and p53 in estrogen and antiprogestin- induced regression of experimental mouse mammary ductal carcinomas
title_sort p21,p27 and p53 in estrogen and antiprogestin- induced regression of experimental mouse mammary ductal carcinomas
dc.creator.none.fl_str_mv Vanzulli, Silvia
Efeyan, Alejo
Benavides, Fernando
Helguero, Luisa A.
Peters, Giselle
Shen, Jianjun
Conti, Claudio J.
Lanari, Claudia Lee Malvina
Molinolo, Alfredo
author Vanzulli, Silvia
author_facet Vanzulli, Silvia
Efeyan, Alejo
Benavides, Fernando
Helguero, Luisa A.
Peters, Giselle
Shen, Jianjun
Conti, Claudio J.
Lanari, Claudia Lee Malvina
Molinolo, Alfredo
author_role author
author2 Efeyan, Alejo
Benavides, Fernando
Helguero, Luisa A.
Peters, Giselle
Shen, Jianjun
Conti, Claudio J.
Lanari, Claudia Lee Malvina
Molinolo, Alfredo
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Apoptosis
Mammary Neoplasm
Tumor Supressor
Proto-Oncogene Proteins P21
topic Apoptosis
Mammary Neoplasm
Tumor Supressor
Proto-Oncogene Proteins P21
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 Metastatic mammary carcinoma tumor lines 59-2-HI and C7-2-HI originated in female BALB/c mice treated with medroxyprogesterone acetate and are maintained by syngeneic transplantation. Both lines express estrogen (ER) and progesterone receptors (PR) and regress completely after estradiol (E 2 ) or antiprogestin treatment. The BET tumor line, of similar origin and biological features, regresses only after E 2 treatment. To investigate possible differences between E 2 - and antiprogestin-mediated effects we evaluated the morphological features, mitosis and apoptosis, and the differential expression of cell-cycle inhibitors associated with tumor regression. Treatments started when tumors reached 50–100 mm 2 . After 24–96 h, tumors were excised and processed for morphological and immunohistochemical studies. Regression was associated with a significant and early decrease in the number of mitosis and with higher percentages of apoptotic cells. These phenomena were accompanied by an increase in p21 and p27 expression in the E 2 and antiprogestin-responsive lines treated with E 2 , RU 38.486 or ZK 98.299 ( P < 0.05). In BET tumors treated with E 2 , p21 expression remained within basal levels and only p27 increased ( P < 0.05). p53 was low in control 59-2-HI and C7-2-HI tumors and increased after treatment ( P < 0.05) whereas BET untreated tumors already expressed high levels of p53 and MDM2. Although the immunohistochemical findings were compatible with alterations of p53, SSCP evaluation failed to disclose the presence of mutations, suggesting that the defective expression of p21 is related to an impaired p53 pathway. UV irradiation failed to increase p21 expression in BET, but was able to induce p53 and p21 in 59-2-HI and C7-2-HI tumors. The absence of an increased expression of p21 in E 2 -regressing BET lesions suggests that this protein is not necessary for estrogen-induced regression, but may be essential for antiprogestin action. Our results also suggest that p53/MDM2 alterations may be one of the mechanisms responsible for selected hormone resistance in breast carcinomas.
Fil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Efeyan, Alejo. 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: Benavides, Fernando. University of Texas; Estados Unidos
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: Peters, Giselle. 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: Shen, Jianjun. University of Texas; Estados Unidos
Fil: Conti, Claudio J.. University of Texas; 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 Metastatic mammary carcinoma tumor lines 59-2-HI and C7-2-HI originated in female BALB/c mice treated with medroxyprogesterone acetate and are maintained by syngeneic transplantation. Both lines express estrogen (ER) and progesterone receptors (PR) and regress completely after estradiol (E 2 ) or antiprogestin treatment. The BET tumor line, of similar origin and biological features, regresses only after E 2 treatment. To investigate possible differences between E 2 - and antiprogestin-mediated effects we evaluated the morphological features, mitosis and apoptosis, and the differential expression of cell-cycle inhibitors associated with tumor regression. Treatments started when tumors reached 50–100 mm 2 . After 24–96 h, tumors were excised and processed for morphological and immunohistochemical studies. Regression was associated with a significant and early decrease in the number of mitosis and with higher percentages of apoptotic cells. These phenomena were accompanied by an increase in p21 and p27 expression in the E 2 and antiprogestin-responsive lines treated with E 2 , RU 38.486 or ZK 98.299 ( P < 0.05). In BET tumors treated with E 2 , p21 expression remained within basal levels and only p27 increased ( P < 0.05). p53 was low in control 59-2-HI and C7-2-HI tumors and increased after treatment ( P < 0.05) whereas BET untreated tumors already expressed high levels of p53 and MDM2. Although the immunohistochemical findings were compatible with alterations of p53, SSCP evaluation failed to disclose the presence of mutations, suggesting that the defective expression of p21 is related to an impaired p53 pathway. UV irradiation failed to increase p21 expression in BET, but was able to induce p53 and p21 in 59-2-HI and C7-2-HI tumors. The absence of an increased expression of p21 in E 2 -regressing BET lesions suggests that this protein is not necessary for estrogen-induced regression, but may be essential for antiprogestin action. Our results also suggest that p53/MDM2 alterations may be one of the mechanisms responsible for selected hormone resistance in breast carcinomas.
publishDate 2002
dc.date.none.fl_str_mv 2002-12
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/11336/31324
Molinolo, Alfredo; Lanari, Claudia Lee Malvina; Conti, Claudio J.; Shen, Jianjun; Peters, Giselle; Helguero, Luisa A.; et al.; p21,p27 and p53 in estrogen and antiprogestin- induced regression of experimental mouse mammary ductal carcinomas; Oxford University Press; Carcinogenesis; 23; 5; 12-2002; 749-757
0143-3334
1460-2180
CONICET Digital
CONICET
url http://hdl.handle.net/11336/31324
identifier_str_mv Molinolo, Alfredo; Lanari, Claudia Lee Malvina; Conti, Claudio J.; Shen, Jianjun; Peters, Giselle; Helguero, Luisa A.; et al.; p21,p27 and p53 in estrogen and antiprogestin- induced regression of experimental mouse mammary ductal carcinomas; Oxford University Press; Carcinogenesis; 23; 5; 12-2002; 749-757
0143-3334
1460-2180
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://academic.oup.com/carcin/article/23/5/749/2608222
info:eu-repo/semantics/altIdentifier/doi/10.1093/carcin/23.5.749
info:eu-repo/semantics/altIdentifier/pmid/https://www.ncbi.nlm.nih.gov/pubmed/12016147
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
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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 13.070432

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