title: Molecular Characterization of Growth Hormone-producing Tumors in the GC Rat Model of Acromegaly.
abstract: 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.
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Sevilla.|Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla (Spain).
authors.forename: Juan F
authors.initials: JF
authors.lastname: Martín-Rodríguez
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Sevilla.|Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla (Spain).
authors.forename: Jose L
authors.initials: JL
authors.lastname: Muñoz-Bravo
authors.affiliation: Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia; CIBER Fisiopatología de la Obesidad y Nutrición; and Campus de Excelencia Internacional Agroalimentario (ceiA3), 14014 Córdoba, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Ibañez-Costa
authors.affiliation: Centro Nacional de Aceleradores (Universidad de Sevilla/CSIC/Junta de Andalucía), Sevilla, (Spain).
authors.forename: Laura
authors.initials: L
authors.lastname: Fernandez-Maza
authors.affiliation: Centro Nacional de Aceleradores (Universidad de Sevilla/CSIC/Junta de Andalucía), Sevilla, (Spain).
authors.forename: Marcin
authors.initials: M
authors.lastname: Balcerzyk
authors.affiliation: División de Neurociencias. Universidad Pablo de Olavide, Sevilla, (Spain).
authors.forename: Rocío
authors.initials: R
authors.lastname: Leal-Campanario
authors.affiliation: Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia; CIBER Fisiopatología de la Obesidad y Nutrición; and Campus de Excelencia Internacional Agroalimentario (ceiA3), 14014 Córdoba, Spain.
authors.forename: Raúl M
authors.initials: RM
authors.lastname: Luque
authors.affiliation: Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia; CIBER Fisiopatología de la Obesidad y Nutrición; and Campus de Excelencia Internacional Agroalimentario (ceiA3), 14014 Córdoba, Spain.
authors.forename: Justo P
authors.initials: JP
authors.lastname: Castaño
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Sevilla.|Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla (Spain).
authors.forename: Eva
authors.initials: E
authors.lastname: Venegas-Moreno
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Sevilla.|Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla (Spain).
authors.forename: Alfonso
authors.initials: A
authors.lastname: Soto-Moreno
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla (Spain).
authors.forename: Alfonso
authors.initials: A
authors.lastname: Leal-Cerro
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Sevilla.|Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla (Spain).
authors.forename: David A
authors.initials: DA
authors.lastname: Cano
mesh_terms: D000172:Acromegaly / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism* / Q000601:surgery; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18; D020869:Gene Expression Profiling; D013006:Growth Hormone / Q000378:metabolism*; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000150:complications* / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D010641:Phenotype; D049268:Positron-Emission Tomography; D051381:Rats; D014057:Tomography, X-Ray Computed; D014407:Tumor Cells, Cultured
chemical_list: D019788:Fluorodeoxyglucose F18; D013006:Growth Hormone