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Páez-Pereda, M.; Giacomini, D.; Refojo, D.; Nagashima, A.C.; Hopfner, U.; Grübler, Y.; Chervin, A.; Goldberg, V.; Goya, R.; Hentges, S.T.; Low, M.J.; Holsboer, F.; Stalla, G.K.; Arzt, E. "Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk" (2003) Proceedings of the National Academy of Sciences of the United States of America. 100(3):1034-1039
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Abstract:

Pituitary tumor development involves clonal expansion stimulated by hormones and growth factors/cytokines. Using mRNA differential display, we found that the bone morphogenetic protein (BMP inhibitor noggin is down-regulated in prolactinomas from dopamine D2-receptor-deficient mice. BMP-4 is overexpressed in prolactinomas taken from dopamine D2-receptor-deficient female mice, but expression of the highly homologous BMP-2 does not differ in normal pituitary tissue and prolactinomas. BMP-4 is overexpressed in other prolactinoma models, including estradiol-induced rat prolactinomas and human prolactinomas, compared with normal tissue and other pituitary adenoma types (Western blot analysis of 48 tumors). BMP-4 stimulates, and noggin blocks, cell proliferation and the expression of c-Myc in human prolactinomas, whereas BMP-4 has no action in other human pituitary tumors. GH3 cells stably transfected with a dominant negative of Smad4 (Smad4dn; a BMP signal cotransducer) or noggin have reduced tumorigenicity in nude mice. Tumor growth recovered in vivo when the Smad4dn expression was lost, proving that BMP-4/Smad4 are involved in tumor development in vivo. BMP-4 and estrogens act through overlapping intracellular signaling mechanisms on GH3 cell proliferation and c-myc expression: they had additive effects at low concentrations but not at saturating doses, and their action was inhibited by blocking either pathway with the reciprocal antagonist (i.e., BMP-4 with ICI 182780 or 17β-estradiol with Smad4dn). Furthermore, coimmunoprecipitation studies demonstrate that under BMP-4 stimulation Smad4 and Smadl physically interact with the estrogen receptor. This previously undescribed prolactinoma pathogenesis mechanism may participate in tumorigenicity in other cells where estrogens and the type β transforming growth factor family have important roles.

Registro:

Documento: Artículo
Título:Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk
Autor:Páez-Pereda, M.; Giacomini, D.; Refojo, D.; Nagashima, A.C.; Hopfner, U.; Grübler, Y.; Chervin, A.; Goldberg, V.; Goya, R.; Hentges, S.T.; Low, M.J.; Holsboer, F.; Stalla, G.K.; Arzt, E.
Filiación:Max Planck Institute of Psychiatry, Kraepelinstrasse 10, 80804 Munich, Germany
Departamento de Fisiología, Universidad de Buenos Aires, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina
Hospital Santa Lucía, 1232 Buenos Aires, Argentina
Instituto de Investigaciones Medicas, Facultad de Medicina, Universidad de Buenos Aires, Donato Alvarez 3150, 1427 Buenos Aires, Argentina
Inst. for Biochem. Res. of La Plata, Universidad Nacional de La Plata, 1900 La Plata, Argentina
Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97201, United States
Palabras clave:Pituitary neoplasms; Signal transduction; bone morphogenetic protein 4; cytokine; dopamine 2 receptor; estradiol; estrogen receptor; fulvestrant; growth factor; hormone derivative; messenger RNA; noggin; Smad protein; Smad1 protein; transforming growth factor beta; unclassified drug; animal cell; animal experiment; animal model; article; carcinogenicity; cell proliferation; controlled study; down regulation; female; gene overexpression; hypophysis adenoma; hypophysis tumor; mouse; nonhuman; nude mouse; oncogene c myc; pathogenesis; priority journal; prolactinoma; protein protein interaction; signal transduction; tumor growth; Western blotting; Animals; Blotting, Western; Bone Morphogenetic Proteins; Cell Division; DNA-Binding Proteins; Estrogens; Female; Gene Expression Profiling; Heterozygote; Humans; Mice; Mice, Nude; Pituitary Neoplasms; Plasmids; Precipitin Tests; Prolactinoma; Proto-Oncogene Proteins c-myc; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2; Receptors, Estrogen; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Smad4 Protein; Time Factors; Trans-Activators; Transcription Factors; Transfection; Animalia; Mus musculus
Año:2003
Volumen:100
Número:3
Página de inicio:1034
Página de fin:1039
DOI: http://dx.doi.org/10.1073/pnas.0237312100
Título revista:Proceedings of the National Academy of Sciences of the United States of America
Título revista abreviado:Proc. Natl. Acad. Sci. U. S. A.
ISSN:00278424
CODEN:PNASA
CAS:estradiol, 50-28-2; fulvestrant, 129453-61-8; Smad protein, 62395-38-4; Smad1 protein, 444952-89-0; bone morphogenetic protein 4; Bone Morphogenetic Proteins; DNA-Binding Proteins; Estrogens; Madh4 protein, rat; Proto-Oncogene Proteins c-myc; Receptors, Dopamine D2; Receptors, Estrogen; RNA, Messenger; Smad4 Protein; SMAD4 protein, human; Smad4 protein, mouse; Trans-Activators; Transcription Factors
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v100_n3_p1034_PaezPereda

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Citas:

---------- APA ----------
Páez-Pereda, M., Giacomini, D., Refojo, D., Nagashima, A.C., Hopfner, U., Grübler, Y., Chervin, A.,..., Arzt, E. (2003) . Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk. Proceedings of the National Academy of Sciences of the United States of America, 100(3), 1034-1039.
http://dx.doi.org/10.1073/pnas.0237312100
---------- CHICAGO ----------
Páez-Pereda, M., Giacomini, D., Refojo, D., Nagashima, A.C., Hopfner, U., Grübler, Y., et al. "Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk" . Proceedings of the National Academy of Sciences of the United States of America 100, no. 3 (2003) : 1034-1039.
http://dx.doi.org/10.1073/pnas.0237312100
---------- MLA ----------
Páez-Pereda, M., Giacomini, D., Refojo, D., Nagashima, A.C., Hopfner, U., Grübler, Y., et al. "Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk" . Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 3, 2003, pp. 1034-1039.
http://dx.doi.org/10.1073/pnas.0237312100
---------- VANCOUVER ----------
Páez-Pereda, M., Giacomini, D., Refojo, D., Nagashima, A.C., Hopfner, U., Grübler, Y., et al. Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk. Proc. Natl. Acad. Sci. U. S. A. 2003;100(3):1034-1039.
http://dx.doi.org/10.1073/pnas.0237312100