Giacomini, D.; Páez-Pereda, M.; Theodoropoulou, M.; Labeur, M.; Refojo, D.; Gerez, J.; Chervin, A.; Berner, S.; Losa, M.; Buchfelder, M.; Renner, U.; Stalla, G.K.; Arzt, E. "Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action" (2006) Endocrinology. 147(1):247-256
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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. Copyright © 2006 by The Endocrine Society.


Documento: Artículo
Título:Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action
Autor:Giacomini, D.; Páez-Pereda, M.; Theodoropoulou, M.; Labeur, M.; Refojo, D.; Gerez, J.; Chervin, A.; Berner, S.; Losa, M.; Buchfelder, M.; Renner, U.; Stalla, G.K.; Arzt, E.
Filiación:Laboratorio de Fisiología Y Biología Molecular, Departamento de Fisiología, Biología Molecular Y Celular, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Max-Planck Institute of Psychiatry, 80804 Munich, Germany
Hospital Santa Lucía, 1232 Buenos Aires, Argentina
Department of Neurosurgery, Ospedale San Raffaele Instituto di Ricovero e Cura a Carattere Scientifico, 20132 Milan, Italy
Department of Neurosurgery, University of Gottingen Medical School, 37075 Gottingen, Germany
Affectis Pharmaceuticals, 80804 Munich, Germany
Laboratorio de Fisiología Y Biología Molecular, Departemento de Fisiología, Biología Molecular Y Celular, Pabellon II, 1428 Buenos Aires, Argentina
Inst. de Fis., Biologia Molecular Y Neuro Ciencias-Argentine National Research Council (CONICET), Argentina
Palabras clave:bone morphogenetic protein 4; corticotropin; noggin; retinoic acid; Smad4 protein; adenohypophysis; animal cell; animal experiment; animal model; animal tissue; article; cancer inhibition; carcinogenicity; cell line; cell proliferation; comparative study; controlled study; corticotropin release; Cushing disease; disease course; enzyme inhibition; genetic transfection; human; human tissue; mouse; nonhuman; priority journal; protein expression; signal transduction; transcription initiation; Adenoma; Animals; Bone Morphogenetic Proteins; Cell Division; Cell Line, Tumor; Cushing Syndrome; Humans; Immunohistochemistry; Mice; Pituitary Gland; Pituitary Neoplasms; Reference Values; Tretinoin
Página de inicio:247
Página de fin:256
Título revista:Endocrinology
Título revista abreviado:Endocrinology
CAS:Smad4 protein, 282562-18-9; corticotropin, 11136-52-0, 9002-60-2, 9061-27-2; retinoic acid, 302-79-4; Bone Morphogenetic Proteins; Tretinoin, 302-79-4; bone morphogenetic protein 4


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---------- APA ----------
Giacomini, D., Páez-Pereda, M., Theodoropoulou, M., Labeur, M., Refojo, D., Gerez, J., Chervin, A.,..., Arzt, E. (2006) . Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action. Endocrinology, 147(1), 247-256.
---------- CHICAGO ----------
Giacomini, D., Páez-Pereda, M., Theodoropoulou, M., Labeur, M., Refojo, D., Gerez, J., et al. "Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action" . Endocrinology 147, no. 1 (2006) : 247-256.
---------- MLA ----------
Giacomini, D., Páez-Pereda, M., Theodoropoulou, M., Labeur, M., Refojo, D., Gerez, J., et al. "Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action" . Endocrinology, vol. 147, no. 1, 2006, pp. 247-256.
---------- VANCOUVER ----------
Giacomini, D., Páez-Pereda, M., Theodoropoulou, M., Labeur, M., Refojo, D., Gerez, J., et al. Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action. Endocrinology. 2006;147(1):247-256.