Artículo

Bottino, M.C.; Cerliani, J.P.; Rojas, P.; Giulianelli, S.; Soldati, R.; Mondillo, C.; Gorostiaga, M.A.; Pignataro, O.P.; Calvo, J.C.; Gutkind, J.S.; Amornphimoltham, P.; Molinolo, A.A.; Lüthy, I.A.; Lanari, C. "Classical membrane progesterone receptors in murine mammary carcinomas: Agonistic effects of progestins and RU-486 mediating rapid non-genomic effects" (2011) Breast Cancer Research and Treatment. 126(3):621-636
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Abstract:

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.

Registro:

Documento: Artículo
Título:Classical membrane progesterone receptors in murine mammary carcinomas: Agonistic effects of progestins and RU-486 mediating rapid non-genomic effects
Autor:Bottino, M.C.; Cerliani, J.P.; Rojas, P.; Giulianelli, S.; Soldati, R.; Mondillo, C.; Gorostiaga, M.A.; Pignataro, O.P.; Calvo, J.C.; Gutkind, J.S.; Amornphimoltham, P.; Molinolo, A.A.; Lüthy, I.A.; Lanari, C.
Filiación:Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas - CONICET, Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina
Laboratorio de Hormonas y Cáncer, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas - CONICET, Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States
Palabras clave: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
Año:2011
Volumen:126
Número:3
Página de inicio:621
Página de fin:636
DOI: http://dx.doi.org/10.1007/s10549-010-0971-3
Título revista:Breast Cancer Research and Treatment
Título revista abreviado:Breast Cancer Res. Treat.
ISSN:01676806
CODEN:BCTRD
CAS:2 (2 amino 3 methoxyphenyl)chromone, 167869-21-8; DNA, 9007-49-2; hydroxytamoxifen, 68047-06-3; medroxyprogesterone acetate, 71-58-9; mifepristone, 84371-65-3; mitogen activated protein kinase, 142243-02-5; thromboplastin, 9035-58-9; Medroxyprogesterone Acetate, 71-58-9; Mifepristone, 84371-65-3; Progestins; Receptors, Progesterone; Steroids
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01676806_v126_n3_p621_Bottino

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Citas:

---------- APA ----------
Bottino, M.C., Cerliani, J.P., Rojas, P., Giulianelli, S., Soldati, R., Mondillo, C., Gorostiaga, M.A.,..., Lanari, C. (2011) . Classical membrane progesterone receptors in murine mammary carcinomas: Agonistic effects of progestins and RU-486 mediating rapid non-genomic effects. Breast Cancer Research and Treatment, 126(3), 621-636.
http://dx.doi.org/10.1007/s10549-010-0971-3
---------- CHICAGO ----------
Bottino, M.C., Cerliani, J.P., Rojas, P., Giulianelli, S., Soldati, R., Mondillo, C., et al. "Classical membrane progesterone receptors in murine mammary carcinomas: Agonistic effects of progestins and RU-486 mediating rapid non-genomic effects" . Breast Cancer Research and Treatment 126, no. 3 (2011) : 621-636.
http://dx.doi.org/10.1007/s10549-010-0971-3
---------- MLA ----------
Bottino, M.C., Cerliani, J.P., Rojas, P., Giulianelli, S., Soldati, R., Mondillo, C., et al. "Classical membrane progesterone receptors in murine mammary carcinomas: Agonistic effects of progestins and RU-486 mediating rapid non-genomic effects" . Breast Cancer Research and Treatment, vol. 126, no. 3, 2011, pp. 621-636.
http://dx.doi.org/10.1007/s10549-010-0971-3
---------- VANCOUVER ----------
Bottino, M.C., Cerliani, J.P., Rojas, P., Giulianelli, S., Soldati, R., Mondillo, C., et al. Classical membrane progesterone receptors in murine mammary carcinomas: Agonistic effects of progestins and RU-486 mediating rapid non-genomic effects. Breast Cancer Res. Treat. 2011;126(3):621-636.
http://dx.doi.org/10.1007/s10549-010-0971-3