Bone Morphogenetic Protein-4 Inhibits Corticotroph Tumor Cells: Involvement in the Retinoic Acid Inhibitory Action

Autores
Giacomini, Damiana Paula; Páez Pereda, Marcelo; Theodoropoulou, Marily; Labeur, Marta; Refojo, Damian; Gerez, Juan Atilio; Chervin, Alberto; Berner, Silvia; Losa, Marco; Buchfelder, Michael; Renner, Ulrich; Stalla, Günter K.; Arzt, Eduardo Simon
Año de publicación
2006
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The molecular mechanisms governing the pathogenesis of ACTH-secreting pituitary adenomas are still obscure. Furthermore, the pharmacological treatment of these tumors is limited. In this study, we report that bone morphogenetic protein-4 (BMP-4) is expressed in the corticotrophs of human normal adenohypophysis and its expression is reduced in corticotrophinomas obtained from Cushing's patients compared with the normal pituitary. BMP-4 treatment of AtT-20 mouse corticotrophinoma cells has an inhibitory effect on ACTH secretion and cell proliferation. AtT-20 cells stably transfected with a dominant-negative form of the BMP-4 signal cotransducer Smad-4 or the BMP-4 inhibitor noggin have increased tumorigenicity in nude mice, showing that BMP-4 has an inhibitory role on corticotroph tumorigenesis in vivo. Because the activation of the retinoic acid receptor has an inhibitory action on Cushing's disease progression, we analyzed the putative interaction of these two pathways. Indeed, retinoic acid induces both BMP-4 transcription and expression and its antiproliferative action is blocked in Smad-4dn- and noggin-transfected Att-20 cells that do not respond to BMP-4. Therefore, retinoic acid induces BMP-4, which participates in the antiproliferative effects of retinoic acid. This new mechanism is a potential target for therapeutic approaches for Cushing's disease.
Fil: Giacomini, Damiana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina
Fil: Páez Pereda, Marcelo. Max Planck Institute of Psychiatry; Alemania. Affectis Pharmaceuticals; Alemania
Fil: Theodoropoulou, Marily. Max Planck Institute of Psychiatry; Alemania
Fil: Labeur, Marta. Max Planck Institute of Psychiatry; Alemania
Fil: Refojo, Damian. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina
Fil: Gerez, Juan Atilio. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina
Fil: Chervin, Alberto. Hospital Santa Lucía; Argentina
Fil: Berner, Silvia. Hospital Santa Lucía; Argentina
Fil: Losa, Marco. Max Planck Institute of Psychiatry; Alemania
Fil: Buchfelder, Michael. University of Gottingen Medical School; Alemania
Fil: Renner, Ulrich. Max Planck Institute of Psychiatry; Alemania
Fil: Stalla, Günter K.. Max Planck Institute of Psychiatry; Alemania
Fil: Arzt, Eduardo Simon. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina
Materia
Retinoic Acid
Tumor Cells
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:11336/44649
Acceder
id CONICETDig_73e8c51e1bad76a18bb0999135b696c2
oai_identifier_str oai:ri.conicet.gov.ar:11336/44649
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Bone Morphogenetic Protein-4 Inhibits Corticotroph Tumor Cells: Involvement in the Retinoic Acid Inhibitory ActionGiacomini, Damiana PaulaPáez Pereda, MarceloTheodoropoulou, MarilyLabeur, MartaRefojo, DamianGerez, Juan AtilioChervin, AlbertoBerner, SilviaLosa, MarcoBuchfelder, MichaelRenner, UlrichStalla, Günter K.Arzt, Eduardo SimonRetinoic AcidTumor CellsThe molecular mechanisms governing the pathogenesis of ACTH-secreting pituitary adenomas are still obscure. Furthermore, the pharmacological treatment of these tumors is limited. In this study, we report that bone morphogenetic protein-4 (BMP-4) is expressed in the corticotrophs of human normal adenohypophysis and its expression is reduced in corticotrophinomas obtained from Cushing's patients compared with the normal pituitary. BMP-4 treatment of AtT-20 mouse corticotrophinoma cells has an inhibitory effect on ACTH secretion and cell proliferation. AtT-20 cells stably transfected with a dominant-negative form of the BMP-4 signal cotransducer Smad-4 or the BMP-4 inhibitor noggin have increased tumorigenicity in nude mice, showing that BMP-4 has an inhibitory role on corticotroph tumorigenesis in vivo. Because the activation of the retinoic acid receptor has an inhibitory action on Cushing's disease progression, we analyzed the putative interaction of these two pathways. Indeed, retinoic acid induces both BMP-4 transcription and expression and its antiproliferative action is blocked in Smad-4dn- and noggin-transfected Att-20 cells that do not respond to BMP-4. Therefore, retinoic acid induces BMP-4, which participates in the antiproliferative effects of retinoic acid. This new mechanism is a potential target for therapeutic approaches for Cushing's disease.Fil: Giacomini, Damiana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaFil: Páez Pereda, Marcelo. Max Planck Institute of Psychiatry; Alemania. Affectis Pharmaceuticals; AlemaniaFil: Theodoropoulou, Marily. Max Planck Institute of Psychiatry; AlemaniaFil: Labeur, Marta. Max Planck Institute of Psychiatry; AlemaniaFil: Refojo, Damian. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaFil: Gerez, Juan Atilio. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaFil: Chervin, Alberto. Hospital Santa Lucía; ArgentinaFil: Berner, Silvia. Hospital Santa Lucía; ArgentinaFil: Losa, Marco. Max Planck Institute of Psychiatry; AlemaniaFil: Buchfelder, Michael. University of Gottingen Medical School; AlemaniaFil: Renner, Ulrich. Max Planck Institute of Psychiatry; AlemaniaFil: Stalla, Günter K.. Max Planck Institute of Psychiatry; AlemaniaFil: Arzt, Eduardo Simon. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaEndocrine Society2006-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/44649Giacomini, Damiana Paula; Páez Pereda, Marcelo; Theodoropoulou, Marily; Labeur, Marta; Refojo, Damian; et al.; Bone Morphogenetic Protein-4 Inhibits Corticotroph Tumor Cells: Involvement in the Retinoic Acid Inhibitory Action; Endocrine Society; Endocrinology; 147; 1; 1-2006; 247-2560013-72271945-7170CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/article/147/1/247/2500409info:eu-repo/semantics/altIdentifier/doi/10.1210/en.2005-0958info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:52Zoai:ri.conicet.gov.ar:11336/44649instacron: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 10:11:52.366CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Bone Morphogenetic Protein-4 Inhibits Corticotroph Tumor Cells: Involvement in the Retinoic Acid Inhibitory Action
title Bone Morphogenetic Protein-4 Inhibits Corticotroph Tumor Cells: Involvement in the Retinoic Acid Inhibitory Action
spellingShingle Bone Morphogenetic Protein-4 Inhibits Corticotroph Tumor Cells: Involvement in the Retinoic Acid Inhibitory Action
Giacomini, Damiana Paula
Retinoic Acid
Tumor Cells
title_short Bone Morphogenetic Protein-4 Inhibits Corticotroph Tumor Cells: Involvement in the Retinoic Acid Inhibitory Action
title_full Bone Morphogenetic Protein-4 Inhibits Corticotroph Tumor Cells: Involvement in the Retinoic Acid Inhibitory Action
title_fullStr Bone Morphogenetic Protein-4 Inhibits Corticotroph Tumor Cells: Involvement in the Retinoic Acid Inhibitory Action
title_full_unstemmed Bone Morphogenetic Protein-4 Inhibits Corticotroph Tumor Cells: Involvement in the Retinoic Acid Inhibitory Action
title_sort Bone Morphogenetic Protein-4 Inhibits Corticotroph Tumor Cells: Involvement in the Retinoic Acid Inhibitory Action
dc.creator.none.fl_str_mv Giacomini, Damiana Paula
Páez Pereda, Marcelo
Theodoropoulou, Marily
Labeur, Marta
Refojo, Damian
Gerez, Juan Atilio
Chervin, Alberto
Berner, Silvia
Losa, Marco
Buchfelder, Michael
Renner, Ulrich
Stalla, Günter K.
Arzt, Eduardo Simon
author Giacomini, Damiana Paula
author_facet Giacomini, Damiana Paula
Páez Pereda, Marcelo
Theodoropoulou, Marily
Labeur, Marta
Refojo, Damian
Gerez, Juan Atilio
Chervin, Alberto
Berner, Silvia
Losa, Marco
Buchfelder, Michael
Renner, Ulrich
Stalla, Günter K.
Arzt, Eduardo Simon
author_role author
author2 Páez Pereda, Marcelo
Theodoropoulou, Marily
Labeur, Marta
Refojo, Damian
Gerez, Juan Atilio
Chervin, Alberto
Berner, Silvia
Losa, Marco
Buchfelder, Michael
Renner, Ulrich
Stalla, Günter K.
Arzt, Eduardo Simon
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Retinoic Acid
Tumor Cells
topic Retinoic Acid
Tumor Cells
dc.description.none.fl_txt_mv The molecular mechanisms governing the pathogenesis of ACTH-secreting pituitary adenomas are still obscure. Furthermore, the pharmacological treatment of these tumors is limited. In this study, we report that bone morphogenetic protein-4 (BMP-4) is expressed in the corticotrophs of human normal adenohypophysis and its expression is reduced in corticotrophinomas obtained from Cushing's patients compared with the normal pituitary. BMP-4 treatment of AtT-20 mouse corticotrophinoma cells has an inhibitory effect on ACTH secretion and cell proliferation. AtT-20 cells stably transfected with a dominant-negative form of the BMP-4 signal cotransducer Smad-4 or the BMP-4 inhibitor noggin have increased tumorigenicity in nude mice, showing that BMP-4 has an inhibitory role on corticotroph tumorigenesis in vivo. Because the activation of the retinoic acid receptor has an inhibitory action on Cushing's disease progression, we analyzed the putative interaction of these two pathways. Indeed, retinoic acid induces both BMP-4 transcription and expression and its antiproliferative action is blocked in Smad-4dn- and noggin-transfected Att-20 cells that do not respond to BMP-4. Therefore, retinoic acid induces BMP-4, which participates in the antiproliferative effects of retinoic acid. This new mechanism is a potential target for therapeutic approaches for Cushing's disease.
Fil: Giacomini, Damiana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina
Fil: Páez Pereda, Marcelo. Max Planck Institute of Psychiatry; Alemania. Affectis Pharmaceuticals; Alemania
Fil: Theodoropoulou, Marily. Max Planck Institute of Psychiatry; Alemania
Fil: Labeur, Marta. Max Planck Institute of Psychiatry; Alemania
Fil: Refojo, Damian. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina
Fil: Gerez, Juan Atilio. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina
Fil: Chervin, Alberto. Hospital Santa Lucía; Argentina
Fil: Berner, Silvia. Hospital Santa Lucía; Argentina
Fil: Losa, Marco. Max Planck Institute of Psychiatry; Alemania
Fil: Buchfelder, Michael. University of Gottingen Medical School; Alemania
Fil: Renner, Ulrich. Max Planck Institute of Psychiatry; Alemania
Fil: Stalla, Günter K.. Max Planck Institute of Psychiatry; Alemania
Fil: Arzt, Eduardo Simon. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina
description The molecular mechanisms governing the pathogenesis of ACTH-secreting pituitary adenomas are still obscure. Furthermore, the pharmacological treatment of these tumors is limited. In this study, we report that bone morphogenetic protein-4 (BMP-4) is expressed in the corticotrophs of human normal adenohypophysis and its expression is reduced in corticotrophinomas obtained from Cushing's patients compared with the normal pituitary. BMP-4 treatment of AtT-20 mouse corticotrophinoma cells has an inhibitory effect on ACTH secretion and cell proliferation. AtT-20 cells stably transfected with a dominant-negative form of the BMP-4 signal cotransducer Smad-4 or the BMP-4 inhibitor noggin have increased tumorigenicity in nude mice, showing that BMP-4 has an inhibitory role on corticotroph tumorigenesis in vivo. Because the activation of the retinoic acid receptor has an inhibitory action on Cushing's disease progression, we analyzed the putative interaction of these two pathways. Indeed, retinoic acid induces both BMP-4 transcription and expression and its antiproliferative action is blocked in Smad-4dn- and noggin-transfected Att-20 cells that do not respond to BMP-4. Therefore, retinoic acid induces BMP-4, which participates in the antiproliferative effects of retinoic acid. This new mechanism is a potential target for therapeutic approaches for Cushing's disease.
publishDate 2006
dc.date.none.fl_str_mv 2006-01
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/11336/44649
Giacomini, Damiana Paula; Páez Pereda, Marcelo; Theodoropoulou, Marily; Labeur, Marta; Refojo, Damian; et al.; Bone Morphogenetic Protein-4 Inhibits Corticotroph Tumor Cells: Involvement in the Retinoic Acid Inhibitory Action; Endocrine Society; Endocrinology; 147; 1; 1-2006; 247-256
0013-7227
1945-7170
CONICET Digital
CONICET
url http://hdl.handle.net/11336/44649
identifier_str_mv Giacomini, Damiana Paula; Páez Pereda, Marcelo; Theodoropoulou, Marily; Labeur, Marta; Refojo, Damian; et al.; Bone Morphogenetic Protein-4 Inhibits Corticotroph Tumor Cells: Involvement in the Retinoic Acid Inhibitory Action; Endocrine Society; Endocrinology; 147; 1; 1-2006; 247-256
0013-7227
1945-7170
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/endo/article/147/1/247/2500409
info:eu-repo/semantics/altIdentifier/doi/10.1210/en.2005-0958
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
dc.publisher.none.fl_str_mv Endocrine Society
publisher.none.fl_str_mv Endocrine Society
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
_version_ 1842270173972660224
score 13.13397

Publicaciones similares