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Sci Rep. 2015 Nov 9;5:16298. doi: 10.1038/srep16298.

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

Author information

1
Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Sevilla.
2
Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla (Spain).
3
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.
4
Centro Nacional de Aceleradores (Universidad de Sevilla/CSIC/Junta de Andalucía), Sevilla, (Spain).
5
División de Neurociencias. Universidad Pablo de Olavide, Sevilla, (Spain).

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.

PMID:
26549306
PMCID:
PMC4637865
DOI:
10.1038/srep16298
[Indexed for MEDLINE]
Free PMC Article

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