New mechanisms involved in the pathogenesis of pituitary adenomas
We studied Smad-4dn tumors generated from lactosomatotrophic GH3 cells stably transfected with a dominant negative form of Smad-4 (a bone morphogenetic protein-4, BMP-4, signal co-transducer) which had reduced tumorigenicity in nude mice, but had showed a late increase in tumor size. We found that t...
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todo:paper_00257680_v63_n2_p147_Giacomini2023-10-03T14:36:38Z New mechanisms involved in the pathogenesis of pituitary adenomas Giacomini, D. Paez-Pereda, M. Refojo, D. Nagashima, A.C. Chervin, A. Goldberg, V. Arzt, E. c-Myc Proclatinoma bone morphogenetic protein 4 estradiol estrogen receptor alpha estrogen receptor beta fulvestrant Myc protein Smad protein animal experiment animal model article carcinogenicity controlled study gene overexpression genetic transfection hypophysis adenoma immunoprecipitation in vivo study mouse nonhuman nude mouse pathogenesis prolactinoma protein expression protein function protein protein interaction regulatory mechanism somatic cell tumor volume Animals Bone Morphogenetic Proteins Cell Division DNA-Binding Proteins Humans Mice Mice, Nude Pituitary Neoplasms Prolactinoma Proto-Oncogene Proteins c-myc Signal Transduction Smad4 Protein Trans-Activators We studied Smad-4dn tumors generated from lactosomatotrophic GH3 cells stably transfected with a dominant negative form of Smad-4 (a bone morphogenetic protein-4, BMP-4, signal co-transducer) which had reduced tumorigenicity in nude mice, but had showed a late increase in tumor size. We found that they had lost in vivo the expression of Smad-4dn and had recovered c-Myc expression. In accordance, BMP-4 is overexpressed and stimulates the expression of c-Myc in human prolactinomas, but not in other human pituitary adenomas or normal pituitary. In adittion ICI 182,780 inhibited BMP-4 stimulated c-Myc expression and BMP-4 and 17β-estradiol in combination had an additive effect on GH3 cell proliferation. Their action was inhibited by blocking BMP-4 with ICI 182,780 or 17β-estradiol with Smad-4dn. Furthermore, co-immunoprecipitation studies demonstrate that Smad-4 physically interacts with the ERα/ERβ. We show for the first time the role of BMP-4 in prolactinoma pathogenesis, involving a functional cross-talk BMP-4/E2. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00257680_v63_n2_p147_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 |
c-Myc Proclatinoma bone morphogenetic protein 4 estradiol estrogen receptor alpha estrogen receptor beta fulvestrant Myc protein Smad protein animal experiment animal model article carcinogenicity controlled study gene overexpression genetic transfection hypophysis adenoma immunoprecipitation in vivo study mouse nonhuman nude mouse pathogenesis prolactinoma protein expression protein function protein protein interaction regulatory mechanism somatic cell tumor volume Animals Bone Morphogenetic Proteins Cell Division DNA-Binding Proteins Humans Mice Mice, Nude Pituitary Neoplasms Prolactinoma Proto-Oncogene Proteins c-myc Signal Transduction Smad4 Protein Trans-Activators |
| spellingShingle |
c-Myc Proclatinoma bone morphogenetic protein 4 estradiol estrogen receptor alpha estrogen receptor beta fulvestrant Myc protein Smad protein animal experiment animal model article carcinogenicity controlled study gene overexpression genetic transfection hypophysis adenoma immunoprecipitation in vivo study mouse nonhuman nude mouse pathogenesis prolactinoma protein expression protein function protein protein interaction regulatory mechanism somatic cell tumor volume Animals Bone Morphogenetic Proteins Cell Division DNA-Binding Proteins Humans Mice Mice, Nude Pituitary Neoplasms Prolactinoma Proto-Oncogene Proteins c-myc Signal Transduction Smad4 Protein Trans-Activators Giacomini, D. Paez-Pereda, M. Refojo, D. Nagashima, A.C. Chervin, A. Goldberg, V. Arzt, E. New mechanisms involved in the pathogenesis of pituitary adenomas |
| topic_facet |
c-Myc Proclatinoma bone morphogenetic protein 4 estradiol estrogen receptor alpha estrogen receptor beta fulvestrant Myc protein Smad protein animal experiment animal model article carcinogenicity controlled study gene overexpression genetic transfection hypophysis adenoma immunoprecipitation in vivo study mouse nonhuman nude mouse pathogenesis prolactinoma protein expression protein function protein protein interaction regulatory mechanism somatic cell tumor volume Animals Bone Morphogenetic Proteins Cell Division DNA-Binding Proteins Humans Mice Mice, Nude Pituitary Neoplasms Prolactinoma Proto-Oncogene Proteins c-myc Signal Transduction Smad4 Protein Trans-Activators |
| description |
We studied Smad-4dn tumors generated from lactosomatotrophic GH3 cells stably transfected with a dominant negative form of Smad-4 (a bone morphogenetic protein-4, BMP-4, signal co-transducer) which had reduced tumorigenicity in nude mice, but had showed a late increase in tumor size. We found that they had lost in vivo the expression of Smad-4dn and had recovered c-Myc expression. In accordance, BMP-4 is overexpressed and stimulates the expression of c-Myc in human prolactinomas, but not in other human pituitary adenomas or normal pituitary. In adittion ICI 182,780 inhibited BMP-4 stimulated c-Myc expression and BMP-4 and 17β-estradiol in combination had an additive effect on GH3 cell proliferation. Their action was inhibited by blocking BMP-4 with ICI 182,780 or 17β-estradiol with Smad-4dn. Furthermore, co-immunoprecipitation studies demonstrate that Smad-4 physically interacts with the ERα/ERβ. We show for the first time the role of BMP-4 in prolactinoma pathogenesis, involving a functional cross-talk BMP-4/E2. |
| format |
JOUR |
| author |
Giacomini, D. Paez-Pereda, M. Refojo, D. Nagashima, A.C. Chervin, A. Goldberg, V. Arzt, E. |
| author_facet |
Giacomini, D. Paez-Pereda, M. Refojo, D. Nagashima, A.C. Chervin, A. Goldberg, V. Arzt, E. |
| author_sort |
Giacomini, D. |
| title |
New mechanisms involved in the pathogenesis of pituitary adenomas |
| title_short |
New mechanisms involved in the pathogenesis of pituitary adenomas |
| title_full |
New mechanisms involved in the pathogenesis of pituitary adenomas |
| title_fullStr |
New mechanisms involved in the pathogenesis of pituitary adenomas |
| title_full_unstemmed |
New mechanisms involved in the pathogenesis of pituitary adenomas |
| title_sort |
new mechanisms involved in the pathogenesis of pituitary adenomas |
| url |
http://hdl.handle.net/20.500.12110/paper_00257680_v63_n2_p147_Giacomini |
| work_keys_str_mv |
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1782025396565311488 |