Classical membrane progesterone receptors in murine mammary carcinomas: Agonistic effects of progestins and RU-486 mediating rapid non-genomic effects
In this article, we demonstrate the expression of functional progesterone binding sites at the cell membrane in murine mammary carcinomas that are stimulated by progestins and inhibited by antiprogestins. Using confocal immunofluorescence, ligand binding and cell compartment-specific western blots,...
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2011
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01676806_v126_n3_p621_Bottino http://hdl.handle.net/20.500.12110/paper_01676806_v126_n3_p621_Bottino |
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paper:paper_01676806_v126_n3_p621_Bottino2023-06-08T15:16:41Z Classical membrane progesterone receptors in murine mammary carcinomas: Agonistic effects of progestins and RU-486 mediating rapid non-genomic effects Bottino, María Cecilia Giulianelli, Sebastián Jesús Mondillo, Carolina Gorostiaga, María A. Pignataro, Omar Pedro Calvo, Juan Carlos Lüthy, Isabel Alicia Lanari, Claudia Lee Malvina Antiprogestins Breast cancer treatment Mammary carcinomas Membrane progesterone receptors Non-genomic effects Progesterone receptor isoforms: Membrane-initiated steroid signaling Progestins 2 (2 amino 3 methoxyphenyl)chromone cyclin D1 DNA hydroxytamoxifen medroxyprogesterone acetate mifepristone mitogen activated protein kinase progesterone receptor thromboplastin animal experiment animal model animal tissue article binding site breast carcinoma cancer growth cancer regression cell membrane cell proliferation concentration response controlled study drug dose comparison drug effect enzyme activation female human human cell immunofluorescence test in vitro study in vivo study ligand binding mouse nonhuman nucleotide sequence priority journal protein DNA binding protein expression Western blotting Animals Female Gene Expression Regulation, Neoplastic Mammary Neoplasms, Animal Medroxyprogesterone Acetate Mice Mice, Inbred BALB C Microscopy, Confocal Microscopy, Fluorescence Mifepristone Neoplasm Transplantation Progestins Receptors, Progesterone Steroids In this article, we demonstrate the expression of functional progesterone binding sites at the cell membrane in murine mammary carcinomas that are stimulated by progestins and inhibited by antiprogestins. Using confocal immunofluorescence, ligand binding and cell compartment-specific western blots, we were able to identify the presence of the classical progesterone receptors. Medrox-yprogesterone acetate (MPA) and RU-486 (1 × 10-11 and 1 × 10-8 M) behaved as agonists activating extracellular signal-regulated kinases (ERKs) and progestin-regulated proteins, except for Cyclin D1 and Tissue factor which failed to increase with 1 × 10 -8 M RU-486, an experimental condition that allows PR to bind DNA. These results predicted a full agonist effect at low concentrations of RU-486. Accordingly, at concentrations lower than 1 × 10-11 M, RU-486 increased cell proliferation in vitro. This effect was abolished by incubation with the ERK kinase inhibitor PD 98059 or by OH-tamoxifen. In vivo, at a daily dose of 1.2 μg/kg body weight RU-486 increased tumor growth, whereas at 12 mg/kg induces tumor regression. Our results indicate that low concentrations of MPA and RU-486 induce similar agonistic non-genomic effects, whereas RU-486 at higher concentrations may inhibit cell proliferation by genomic-induced effects. This suggests that RU-486 should be therapeutically administered at doses high enough to guarantee its genomic inhibitory effect. © Springer Science+Business Media, LLC. 2010. Fil:Bottino, M.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Giulianelli, S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Mondillo, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Gorostiaga, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pignataro, O.P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Calvo, J.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Lüthy, I.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Lanari, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2011 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01676806_v126_n3_p621_Bottino http://hdl.handle.net/20.500.12110/paper_01676806_v126_n3_p621_Bottino |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Antiprogestins Breast cancer treatment Mammary carcinomas Membrane progesterone receptors Non-genomic effects Progesterone receptor isoforms: Membrane-initiated steroid signaling Progestins 2 (2 amino 3 methoxyphenyl)chromone cyclin D1 DNA hydroxytamoxifen medroxyprogesterone acetate mifepristone mitogen activated protein kinase progesterone receptor thromboplastin animal experiment animal model animal tissue article binding site breast carcinoma cancer growth cancer regression cell membrane cell proliferation concentration response controlled study drug dose comparison drug effect enzyme activation female human human cell immunofluorescence test in vitro study in vivo study ligand binding mouse nonhuman nucleotide sequence priority journal protein DNA binding protein expression Western blotting Animals Female Gene Expression Regulation, Neoplastic Mammary Neoplasms, Animal Medroxyprogesterone Acetate Mice Mice, Inbred BALB C Microscopy, Confocal Microscopy, Fluorescence Mifepristone Neoplasm Transplantation Progestins Receptors, Progesterone Steroids |
| spellingShingle |
Antiprogestins Breast cancer treatment Mammary carcinomas Membrane progesterone receptors Non-genomic effects Progesterone receptor isoforms: Membrane-initiated steroid signaling Progestins 2 (2 amino 3 methoxyphenyl)chromone cyclin D1 DNA hydroxytamoxifen medroxyprogesterone acetate mifepristone mitogen activated protein kinase progesterone receptor thromboplastin animal experiment animal model animal tissue article binding site breast carcinoma cancer growth cancer regression cell membrane cell proliferation concentration response controlled study drug dose comparison drug effect enzyme activation female human human cell immunofluorescence test in vitro study in vivo study ligand binding mouse nonhuman nucleotide sequence priority journal protein DNA binding protein expression Western blotting Animals Female Gene Expression Regulation, Neoplastic Mammary Neoplasms, Animal Medroxyprogesterone Acetate Mice Mice, Inbred BALB C Microscopy, Confocal Microscopy, Fluorescence Mifepristone Neoplasm Transplantation Progestins Receptors, Progesterone Steroids Bottino, María Cecilia Giulianelli, Sebastián Jesús Mondillo, Carolina Gorostiaga, María A. Pignataro, Omar Pedro Calvo, Juan Carlos Lüthy, Isabel Alicia Lanari, Claudia Lee Malvina Classical membrane progesterone receptors in murine mammary carcinomas: Agonistic effects of progestins and RU-486 mediating rapid non-genomic effects |
| topic_facet |
Antiprogestins Breast cancer treatment Mammary carcinomas Membrane progesterone receptors Non-genomic effects Progesterone receptor isoforms: Membrane-initiated steroid signaling Progestins 2 (2 amino 3 methoxyphenyl)chromone cyclin D1 DNA hydroxytamoxifen medroxyprogesterone acetate mifepristone mitogen activated protein kinase progesterone receptor thromboplastin animal experiment animal model animal tissue article binding site breast carcinoma cancer growth cancer regression cell membrane cell proliferation concentration response controlled study drug dose comparison drug effect enzyme activation female human human cell immunofluorescence test in vitro study in vivo study ligand binding mouse nonhuman nucleotide sequence priority journal protein DNA binding protein expression Western blotting Animals Female Gene Expression Regulation, Neoplastic Mammary Neoplasms, Animal Medroxyprogesterone Acetate Mice Mice, Inbred BALB C Microscopy, Confocal Microscopy, Fluorescence Mifepristone Neoplasm Transplantation Progestins Receptors, Progesterone Steroids |
| description |
In this article, we demonstrate the expression of functional progesterone binding sites at the cell membrane in murine mammary carcinomas that are stimulated by progestins and inhibited by antiprogestins. Using confocal immunofluorescence, ligand binding and cell compartment-specific western blots, we were able to identify the presence of the classical progesterone receptors. Medrox-yprogesterone acetate (MPA) and RU-486 (1 × 10-11 and 1 × 10-8 M) behaved as agonists activating extracellular signal-regulated kinases (ERKs) and progestin-regulated proteins, except for Cyclin D1 and Tissue factor which failed to increase with 1 × 10 -8 M RU-486, an experimental condition that allows PR to bind DNA. These results predicted a full agonist effect at low concentrations of RU-486. Accordingly, at concentrations lower than 1 × 10-11 M, RU-486 increased cell proliferation in vitro. This effect was abolished by incubation with the ERK kinase inhibitor PD 98059 or by OH-tamoxifen. In vivo, at a daily dose of 1.2 μg/kg body weight RU-486 increased tumor growth, whereas at 12 mg/kg induces tumor regression. Our results indicate that low concentrations of MPA and RU-486 induce similar agonistic non-genomic effects, whereas RU-486 at higher concentrations may inhibit cell proliferation by genomic-induced effects. This suggests that RU-486 should be therapeutically administered at doses high enough to guarantee its genomic inhibitory effect. © Springer Science+Business Media, LLC. 2010. |
| author |
Bottino, María Cecilia Giulianelli, Sebastián Jesús Mondillo, Carolina Gorostiaga, María A. Pignataro, Omar Pedro Calvo, Juan Carlos Lüthy, Isabel Alicia Lanari, Claudia Lee Malvina |
| author_facet |
Bottino, María Cecilia Giulianelli, Sebastián Jesús Mondillo, Carolina Gorostiaga, María A. Pignataro, Omar Pedro Calvo, Juan Carlos Lüthy, Isabel Alicia Lanari, Claudia Lee Malvina |
| author_sort |
Bottino, María Cecilia |
| title |
Classical membrane progesterone receptors in murine mammary carcinomas: Agonistic effects of progestins and RU-486 mediating rapid non-genomic effects |
| title_short |
Classical membrane progesterone receptors in murine mammary carcinomas: Agonistic effects of progestins and RU-486 mediating rapid non-genomic effects |
| title_full |
Classical membrane progesterone receptors in murine mammary carcinomas: Agonistic effects of progestins and RU-486 mediating rapid non-genomic effects |
| title_fullStr |
Classical membrane progesterone receptors in murine mammary carcinomas: Agonistic effects of progestins and RU-486 mediating rapid non-genomic effects |
| title_full_unstemmed |
Classical membrane progesterone receptors in murine mammary carcinomas: Agonistic effects of progestins and RU-486 mediating rapid non-genomic effects |
| title_sort |
classical membrane progesterone receptors in murine mammary carcinomas: agonistic effects of progestins and ru-486 mediating rapid non-genomic effects |
| publishDate |
2011 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01676806_v126_n3_p621_Bottino http://hdl.handle.net/20.500.12110/paper_01676806_v126_n3_p621_Bottino |
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