D.A.C. was supported by the Nicolás Monardes
program of the Andalusian Ministry of Health (C-0015-2014) and by a grant from the Andalusian
Ministry of Science and Innovation (CTS-7478). A.S-M and A.L.C were supported by grants from
the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación co-funded with Fondos
FEDER (PI12/0143 and PI13/02043, respectively) and the Andalusian Regional Government (CTS-444)
and a grant from Pfizer Spain. R.L.C. was supported by a grant from Andalusian Ministry of Health
(PI0302-2012). R.M.L. was supported by grants from Proyecto de Investigación en Salud (FIS) PI13-
00651 (funded by Instituto de Salud Carlos III), CTS-1406, PI-0639-2012, BIO-0139 (funded by Junta
de Andalucía) and by Ayuda Merck Serono 2013. J. P. C. was funded by a grant (BFU2013-43282-R)
from Ministerio de Economía y Competitividad. CIBER is an initiative of Instituto de Salud Carlos III,
Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain. J.F.M.R. is supported by the “Sara Borrell”
program from the Instituto de Salud Carlos III. R.M. Luque and J.P. Castaño have received grants and
lecture fees from Ipsen and Novartis. E. Venegas-Moreno and A. Soto-Moreno received grants and lecture
fees from Ipsen, Novartis and Pfizer. A. Leal-Cerro received grants from Novartis and Pfizer. David
Cano received a grant from Novartis

Balcerzyk, M

Cano, DA

Castano, JP

Fernandez-Maza, L

Ibanez-Costa, A

Leal-Campanario, R

Leal-Cerro, A

Luque, RM

Martin-Rodriguez, JF

Munoz-Bravo, JL

Soto-Moreno, A

Venegas-Moreno, E

Scientific Reports

PubMed

AbstractAcromegaly is a disorder resulting from excessive production of growth hormone (GH) and consequent increase of insulin-like growth factor 1 (IGF-I), most frequently caused by pituitary adenomas. Elevated GH and IGF-I levels results in wide range of somatic, cardiovascular, endocrine, metabolic and gastrointestinal morbidities. Subcutaneous implantation of the GH-secreting GC cell line in rats leads to the formation of tumors. GC tumor-bearing rats develop characteristics that resemble human acromegaly including gigantism and visceromegaly. However, GC tumors remain poorly characterized at a molecular level. In the present work, we report a detailed histological and molecular characterization of GC tumors using immunohistochemistry, molecular biology and imaging techniques. GC tumors display histopathological and molecular features of human GH-producing tumors, including hormone production, cell architecture, senescence activation and alterations in cell cycle gene expression. Furthermore, GC tumors cells displayed sensitivity to somatostatin analogues, drugs that are currently used in the treatment of human GH-producing adenomas, thus supporting the GC tumor model as a translational tool to evaluate therapeutic agents. The information obtained would help to maximize the usefulness of the GC rat model for research and preclinical studies in GH-secreting tumors.</jats:p

Juan F. Martín-Rodríguez

Jose L. Muñoz-Bravo

Alejandro Ibañez-Costa

Laura Fernandez-Maza

Marcin Balcerzyk

Rocío Leal-Campanario

Raúl M. Luque

Justo P. Castaño

Eva Venegas-Moreno

Alfonso Soto-Moreno

Alfonso Leal-Cerro

David A. Cano

Crossref

Molecular Characterization of Growth Hormone-producing Tumors in the GC Rat Model of Acromegaly

Queen Mary Research Online

et al.Acromegaly is a disorder resulting from excessive production of growth hormone (GH) and consequent increase of insulin-like growth factor 1 (IGF-I), most frequently caused by pituitary adenomas. Elevated GH and IGF-I levels results in wide range of somatic, cardiovascular, endocrine, metabolic, and gastrointestinal morbidities. Subcutaneous implantation of the GH-secreting GC cell line in rats leads to the formation of tumors. GC tumor-bearing rats develop characteristics that resemble human acromegaly including gigantism and visceromegaly. However, GC tumors remain poorly characterized at a molecular level. In the present work, we report a detailed histological and molecular characterization of GC tumors using immunohistochemistry, molecular biology and imaging techniques. GC tumors display histopathological and molecular features of human GH-producing tumors, including hormone production, cell architecture, senescence activation and alterations in cell cycle gene expression. Furthermore, GC tumors cells displayed sensitivity to somatostatin analogues, drugs that are currently used in the treatment of human GH-producing adenomas, thus supporting the GC tumor model as a translational tool to evaluate therapeutic agents. The information obtained would help to maximize the usefulness of the GC rat model for research and preclinical studies in GH-secreting tumors.D.A.C. was supported by the Nicolás Monardes program of the Andalusian Ministry of Health (C-0015-2014) and by a grant from the Andalusian Ministry of Science and Innovation (CTS-7478). A.S-M and A.L.C were supported by grants from the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación co-funded with Fondos FEDER (PI12/0143 and PI13/02043, respectively) and the Andalusian Regional Government (CTS-444) and a grant from Pfizer Spain. R.L.C. was supported by a grant from Andalusian Ministry of Health (PI0302-2012). R.M.L. was supported by grants from Proyecto de Investigación en Salud (FIS) PI13-00651 (funded by Instituto de Salud Carlos III), CTS-1406, PI-0639-2012, BIO-0139 (funded by Junta de Andalucía) and by Ayuda Merck Serono 2013. J. P. C. was funded by a grant (BFU2013-43282-R) from Ministerio de Economía y Competitividad. CIBER is an initiative of Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain. J.F.M.R. is supported by the “Sara Borrell” program from the Instituto de Salud Carlos III. R.M. Luque and J.P. Castaño have received grants and lecture fees from Ipsen and Novartis. E. Venegas-Moreno and A. Soto-Moreno received grants and lecture fees from Ipsen, Novartis and Pfizer. A. Leal-Cerro received grants from Novartis and Pfizer. David Cano received a grant from Novartis.Peer Reviewe

Martín-Rodríguez, Juan Francisco

Muñoz-Bravo, José Luis

Fernández-Maza, Laura

Balcerzyk, Marcin

Venegas Moreno, Eva

Soto-Moreno, Alfonso

Leal Cerro, Alfonso

Cano González, David A.

Digital.CSIC

Molecular characterization of growth hormone-producing tumors in the GC rat model of acromegaly

Acromegaly is a disorder resulting from excessive production of growth hormone (GH) and consequent increase of insulin-like growth factor 1 (IGF-I), most frequently caused by pituitary adenomas. Elevated GH and IGF-I levels results in wide range of somatic, cardiovascular, endocrine, metabolic and gastrointestinal morbidities. Subcutaneous implantation of the GH-secreting GC cell line in rats leads to the formation of tumors. GC tumor-bearing rats develop characteristics that resemble human acromegaly including gigantism and visceromegaly. However, GC tumors remain poorly characterized at a molecular level. In the present work, we report a detailed histological and molecular characterization of GC tumors using immunohistochemistry, molecular biology and imaging techniques. GC tumors display histopathological and molecular features of human GH-producing tumors, including hormone production, cell architecture, senescence activation and alterations in cell cycle gene expression. Furthermore, GC tumors cells displayed sensitivity to somatostatin analogues, drugs that are currently used in the treatment of human GH-producing adenomas, thus supporting the GC tumor model as a translational tool to evaluate therapeutic agents. The information obtained would help to maximize the usefulness of the GC rat model for research and preclinical studies in GH-secreting tumors

Molecular Characterization of Growth Hormone-producing Tumors in the GC Rat Model of Acromegaly

Abstract

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Queen Mary Research Online

Digital.CSIC

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