Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins.

Autores
Lanari, Claudia Lee Malvina; Luthy, Isabel Alicia; Lamb, Caroline Ana; Fabris, Victoria Teresa; Pagano, Eleonora Samanta; Helguero, Luisa A.; Sanjuan, Norberto Aníbal; Merani, Susana; Molinolo, Alfredo
Año de publicación
2001
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We have developed an experimental model of mammary carcinogenesis in which the administration of medroxyprogesterone acetate (MPA) to female BALB/c mice induces progestin-dependent ductal metastatic mammary tumors with high levels of estrogen receptor (ER) and progesterone receptor (PR). Through selective transplants in untreated mice, we have obtained progestin-independent variants, still expressing high levels of ER and PR. Primary cultures of the MPA-induced carcinomas C4-HD and C7-HI were set up, and after 3–4 months, several different cell lines were obtained. Four of these, MC4-L1, MC4-L2, MC4-L3, and MC4-L5 were established from C4-HD and a fifth, MC7-L1, from C7-HI. All cells were of epithelial origin, as demonstrated by electron microscopy and by immunocytochemical identification of cytokeratin and cadherin. In vitro MC4-L1, MC4-L3, and MC4-L5 showed a typical epithelial morphology; when transplanted in vivo, they originated metastatic carcinomas with different degrees of differentiation. MC4-L2 and MC7-L1 deviated from the standard epithelial picture; they disclosed a spindle-shaped morphology in vitro and in vivo gave rise to a biphasic spindle cell/tubular carcinoma and an anaplastic carcinoma, respectively; both lines gave rise to metastases. This differential morphology correlated with a higher degree of aggressiveness, as compared with MC4-L1, MC4-L3, and MC4-L5. ERs and PRs were detected by binding, immunocytochemistry, and Western blot. In vitro, MC4-L2 and MC7-L1 were stimulated by MPA (nM to uM) and 17beta-estradiol (nM and 10 nM); no significant stimulation was observed in MC4-L1, MC4-L3, and MC4-L5 under the same experimental conditions. In vivo, MPA significantly stimulated tumor growth in all epithelioid lines but not in MC4-L2 and MC7-L1. A progestin-dependent growth pattern was confirmed for MC4-L1, MC4-L3, and MC4-L5 in successive transplants, whereas MC4-L2 and MC7-L1 behaved as progestin independent. This is the first description of mouse mammary carcinoma cell lines expressing ER and PR. The different in vitro hormone responses as compared with in vivo and the differential effects of 17beta-estradiol in the parental tumors and in cell lines render these lines useful tools for the in vitro and in vivo study of hormone regulation of tumor growth and metastases.
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: Luthy, Isabel Alicia. 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: Lamb, Caroline Ana. 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: Fabris, Victoria Teresa. 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: Pagano, Eleonora Samanta. 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: 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: Sanjuan, Norberto Aníbal. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Merani, Susana. Universidad de Buenos Aires. Facultad de Medicina; 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
Breast Cancer
Carcinoma
Mice
Hormones
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:11336/31322
Acceder
id CONICETDig_9b50ec0ebc409d6858a91122912f5a60
oai_identifier_str oai:ri.conicet.gov.ar:11336/31322
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins.Lanari, Claudia Lee MalvinaLuthy, Isabel AliciaLamb, Caroline AnaFabris, Victoria TeresaPagano, Eleonora SamantaHelguero, Luisa A.Sanjuan, Norberto AníbalMerani, SusanaMolinolo, AlfredoBreast CancerCarcinomaMiceHormoneshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3We have developed an experimental model of mammary carcinogenesis in which the administration of medroxyprogesterone acetate (MPA) to female BALB/c mice induces progestin-dependent ductal metastatic mammary tumors with high levels of estrogen receptor (ER) and progesterone receptor (PR). Through selective transplants in untreated mice, we have obtained progestin-independent variants, still expressing high levels of ER and PR. Primary cultures of the MPA-induced carcinomas C4-HD and C7-HI were set up, and after 3–4 months, several different cell lines were obtained. Four of these, MC4-L1, MC4-L2, MC4-L3, and MC4-L5 were established from C4-HD and a fifth, MC7-L1, from C7-HI. All cells were of epithelial origin, as demonstrated by electron microscopy and by immunocytochemical identification of cytokeratin and cadherin. In vitro MC4-L1, MC4-L3, and MC4-L5 showed a typical epithelial morphology; when transplanted in vivo, they originated metastatic carcinomas with different degrees of differentiation. MC4-L2 and MC7-L1 deviated from the standard epithelial picture; they disclosed a spindle-shaped morphology in vitro and in vivo gave rise to a biphasic spindle cell/tubular carcinoma and an anaplastic carcinoma, respectively; both lines gave rise to metastases. This differential morphology correlated with a higher degree of aggressiveness, as compared with MC4-L1, MC4-L3, and MC4-L5. ERs and PRs were detected by binding, immunocytochemistry, and Western blot. In vitro, MC4-L2 and MC7-L1 were stimulated by MPA (nM to uM) and 17beta-estradiol (nM and 10 nM); no significant stimulation was observed in MC4-L1, MC4-L3, and MC4-L5 under the same experimental conditions. In vivo, MPA significantly stimulated tumor growth in all epithelioid lines but not in MC4-L2 and MC7-L1. A progestin-dependent growth pattern was confirmed for MC4-L1, MC4-L3, and MC4-L5 in successive transplants, whereas MC4-L2 and MC7-L1 behaved as progestin independent. This is the first description of mouse mammary carcinoma cell lines expressing ER and PR. The different in vitro hormone responses as compared with in vivo and the differential effects of 17beta-estradiol in the parental tumors and in cell lines render these lines useful tools for the in vitro and in vivo study of hormone regulation of tumor growth and metastases.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; ArgentinaFil: Luthy, Isabel Alicia. 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: Lamb, Caroline Ana. 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: Fabris, Victoria Teresa. 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: Pagano, Eleonora Samanta. 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: 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: Sanjuan, Norberto Aníbal. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Merani, Susana. Universidad de Buenos Aires. Facultad de Medicina; 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; ArgentinaAmerican Association for Cancer Research2001-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/31322Lanari, Claudia Lee Malvina; Luthy, Isabel Alicia; Lamb, Caroline Ana; Fabris, Victoria Teresa; Pagano, Eleonora Samanta; et al.; Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins.; American Association for Cancer Research; Cancer Research; 61; 1; 12-2001; 293-3020008-5472CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/61/1/293.longinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:58:58Zoai:ri.conicet.gov.ar:11336/31322instacron: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:34982025-09-03 09:58:59.088CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins.
title Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins.
spellingShingle Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins.
Lanari, Claudia Lee Malvina
Breast Cancer
Carcinoma
Mice
Hormones
title_short Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins.
title_full Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins.
title_fullStr Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins.
title_full_unstemmed Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins.
title_sort Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins.
dc.creator.none.fl_str_mv Lanari, Claudia Lee Malvina
Luthy, Isabel Alicia
Lamb, Caroline Ana
Fabris, Victoria Teresa
Pagano, Eleonora Samanta
Helguero, Luisa A.
Sanjuan, Norberto Aníbal
Merani, Susana
Molinolo, Alfredo
author Lanari, Claudia Lee Malvina
author_facet Lanari, Claudia Lee Malvina
Luthy, Isabel Alicia
Lamb, Caroline Ana
Fabris, Victoria Teresa
Pagano, Eleonora Samanta
Helguero, Luisa A.
Sanjuan, Norberto Aníbal
Merani, Susana
Molinolo, Alfredo
author_role author
author2 Luthy, Isabel Alicia
Lamb, Caroline Ana
Fabris, Victoria Teresa
Pagano, Eleonora Samanta
Helguero, Luisa A.
Sanjuan, Norberto Aníbal
Merani, Susana
Molinolo, Alfredo
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Breast Cancer
Carcinoma
Mice
Hormones
topic Breast Cancer
Carcinoma
Mice
Hormones
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 We have developed an experimental model of mammary carcinogenesis in which the administration of medroxyprogesterone acetate (MPA) to female BALB/c mice induces progestin-dependent ductal metastatic mammary tumors with high levels of estrogen receptor (ER) and progesterone receptor (PR). Through selective transplants in untreated mice, we have obtained progestin-independent variants, still expressing high levels of ER and PR. Primary cultures of the MPA-induced carcinomas C4-HD and C7-HI were set up, and after 3–4 months, several different cell lines were obtained. Four of these, MC4-L1, MC4-L2, MC4-L3, and MC4-L5 were established from C4-HD and a fifth, MC7-L1, from C7-HI. All cells were of epithelial origin, as demonstrated by electron microscopy and by immunocytochemical identification of cytokeratin and cadherin. In vitro MC4-L1, MC4-L3, and MC4-L5 showed a typical epithelial morphology; when transplanted in vivo, they originated metastatic carcinomas with different degrees of differentiation. MC4-L2 and MC7-L1 deviated from the standard epithelial picture; they disclosed a spindle-shaped morphology in vitro and in vivo gave rise to a biphasic spindle cell/tubular carcinoma and an anaplastic carcinoma, respectively; both lines gave rise to metastases. This differential morphology correlated with a higher degree of aggressiveness, as compared with MC4-L1, MC4-L3, and MC4-L5. ERs and PRs were detected by binding, immunocytochemistry, and Western blot. In vitro, MC4-L2 and MC7-L1 were stimulated by MPA (nM to uM) and 17beta-estradiol (nM and 10 nM); no significant stimulation was observed in MC4-L1, MC4-L3, and MC4-L5 under the same experimental conditions. In vivo, MPA significantly stimulated tumor growth in all epithelioid lines but not in MC4-L2 and MC7-L1. A progestin-dependent growth pattern was confirmed for MC4-L1, MC4-L3, and MC4-L5 in successive transplants, whereas MC4-L2 and MC7-L1 behaved as progestin independent. This is the first description of mouse mammary carcinoma cell lines expressing ER and PR. The different in vitro hormone responses as compared with in vivo and the differential effects of 17beta-estradiol in the parental tumors and in cell lines render these lines useful tools for the in vitro and in vivo study of hormone regulation of tumor growth and metastases.
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: Luthy, Isabel Alicia. 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: Lamb, Caroline Ana. 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: Fabris, Victoria Teresa. 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: Pagano, Eleonora Samanta. 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: 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: Sanjuan, Norberto Aníbal. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Merani, Susana. Universidad de Buenos Aires. Facultad de Medicina; 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 We have developed an experimental model of mammary carcinogenesis in which the administration of medroxyprogesterone acetate (MPA) to female BALB/c mice induces progestin-dependent ductal metastatic mammary tumors with high levels of estrogen receptor (ER) and progesterone receptor (PR). Through selective transplants in untreated mice, we have obtained progestin-independent variants, still expressing high levels of ER and PR. Primary cultures of the MPA-induced carcinomas C4-HD and C7-HI were set up, and after 3–4 months, several different cell lines were obtained. Four of these, MC4-L1, MC4-L2, MC4-L3, and MC4-L5 were established from C4-HD and a fifth, MC7-L1, from C7-HI. All cells were of epithelial origin, as demonstrated by electron microscopy and by immunocytochemical identification of cytokeratin and cadherin. In vitro MC4-L1, MC4-L3, and MC4-L5 showed a typical epithelial morphology; when transplanted in vivo, they originated metastatic carcinomas with different degrees of differentiation. MC4-L2 and MC7-L1 deviated from the standard epithelial picture; they disclosed a spindle-shaped morphology in vitro and in vivo gave rise to a biphasic spindle cell/tubular carcinoma and an anaplastic carcinoma, respectively; both lines gave rise to metastases. This differential morphology correlated with a higher degree of aggressiveness, as compared with MC4-L1, MC4-L3, and MC4-L5. ERs and PRs were detected by binding, immunocytochemistry, and Western blot. In vitro, MC4-L2 and MC7-L1 were stimulated by MPA (nM to uM) and 17beta-estradiol (nM and 10 nM); no significant stimulation was observed in MC4-L1, MC4-L3, and MC4-L5 under the same experimental conditions. In vivo, MPA significantly stimulated tumor growth in all epithelioid lines but not in MC4-L2 and MC7-L1. A progestin-dependent growth pattern was confirmed for MC4-L1, MC4-L3, and MC4-L5 in successive transplants, whereas MC4-L2 and MC7-L1 behaved as progestin independent. This is the first description of mouse mammary carcinoma cell lines expressing ER and PR. The different in vitro hormone responses as compared with in vivo and the differential effects of 17beta-estradiol in the parental tumors and in cell lines render these lines useful tools for the in vitro and in vivo study of hormone regulation of tumor growth and metastases.
publishDate 2001
dc.date.none.fl_str_mv 2001-12
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/11336/31322
Lanari, Claudia Lee Malvina; Luthy, Isabel Alicia; Lamb, Caroline Ana; Fabris, Victoria Teresa; Pagano, Eleonora Samanta; et al.; Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins.; American Association for Cancer Research; Cancer Research; 61; 1; 12-2001; 293-302
0008-5472
CONICET Digital
CONICET
url http://hdl.handle.net/11336/31322
identifier_str_mv Lanari, Claudia Lee Malvina; Luthy, Isabel Alicia; Lamb, Caroline Ana; Fabris, Victoria Teresa; Pagano, Eleonora Samanta; et al.; Five novel hormone-responsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins.; American Association for Cancer Research; Cancer Research; 61; 1; 12-2001; 293-302
0008-5472
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/61/1/293.long
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
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Association for Cancer Research
publisher.none.fl_str_mv American Association for Cancer Research
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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