Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action
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 aden...
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2006
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00137227_v147_n1_p247_Giacomini http://hdl.handle.net/20.500.12110/paper_00137227_v147_n1_p247_Giacomini |
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paper:paper_00137227_v147_n1_p247_Giacomini2023-06-08T14:36:12Z Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action Giacomini, Damiana Paula Páez Pereda, Marcelo Labeur, Marta Susana Refojo, Damián Gerez, Juan Atilio 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 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. Fil:Giacomini, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Páez-Pereda, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Labeur, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Refojo, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Gerez, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2006 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00137227_v147_n1_p247_Giacomini http://hdl.handle.net/20.500.12110/paper_00137227_v147_n1_p247_Giacomini |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Giacomini, Damiana Paula Páez Pereda, Marcelo Labeur, Marta Susana Refojo, Damián Gerez, Juan Atilio Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action |
| topic_facet |
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 |
| 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. Copyright © 2006 by The Endocrine Society. |
| author |
Giacomini, Damiana Paula Páez Pereda, Marcelo Labeur, Marta Susana Refojo, Damián Gerez, Juan Atilio |
| author_facet |
Giacomini, Damiana Paula Páez Pereda, Marcelo Labeur, Marta Susana Refojo, Damián Gerez, Juan Atilio |
| author_sort |
Giacomini, Damiana Paula |
| title |
Bone morphogenetic protein-4 inhibits corticotroph tumor cells: Involvement in the retinoic acid inhibitory action |
| 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 |
| publishDate |
2006 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00137227_v147_n1_p247_Giacomini http://hdl.handle.net/20.500.12110/paper_00137227_v147_n1_p247_Giacomini |
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| _version_ |
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