Analysis of the Role of Igf2 in Adrenal Tumour Development in Transgenic Mouse Models
| Autor: | Roberto Bandiera, Annabel Berthon, Isabelle Sahut-Barnola, Antoine Martinez, Pierre Val, Cyrille de Joussineau, Jérôme Bertherat, Coralie Drelon, M. Batisse-Lignier, Anne-Marie Lefrançois-Martinez, Frédérique Tissier, Bruno Ragazzon |
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| Přispěvatelé: | Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Cochin [AP-HP], [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) (EMD), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions génétiques et cellulaires au cours de la différenciation, Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, CHU Clermont-Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP] |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Anatomy and Physiology
Tumor Physiology MESH: beta Catenin Adrenal Gland Neoplasms [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] MESH: Insulin-Like Growth Factor II Mice 0302 clinical medicine Endocrinology Molecular Cell Biology Basic Cancer Research Adrenal Glands Signaling in Cellular Processes MESH: Animals MESH: Adrenal Glands Endocrine Tumors Insulin-like Growth Factor beta Catenin ComputingMilieux_MISCELLANEOUS 0303 health sciences Multidisciplinary biology Adrenal cortex Wnt signaling pathway [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Hyperplasia Beta-Catenin Signaling medicine.anatomical_structure Cell Transformation Neoplastic Oncology 030220 oncology & carcinogenesis Disease Progression Medicine MESH: Disease Progression Research Article Signal Transduction Genetically modified mouse medicine.medical_specialty animal structures MESH: Mice Transgenic Science Transgene Adrenal Gland Neoplasm [SDV.CAN]Life Sciences [q-bio]/Cancer Endocrine System Mice Transgenic Signaling Pathways Adrenal Tumors 03 medical and health sciences Catenin Signal Transduction GLI1 Insulin-Like Growth Factor II [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Internal medicine medicine Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Mice Biology 030304 developmental biology Oncogene Endocrine Physiology Cancers and Neoplasms [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology medicine.disease MESH: Adrenal Gland Neoplasms [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics Disease Models Animal [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis MESH: Cell Transformation Neoplastic biology.protein MESH: Disease Models Animal |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2012, 7 (8), pp.e44171. ⟨10.1371/journal.pone.0044171⟩ PLoS ONE, Public Library of Science, 2012, 7 (8), ⟨10.1371/journal.pone.0044171⟩ PLoS ONE, 2012, 7 (8), pp.e44171. ⟨10.1371/journal.pone.0044171⟩ PLoS ONE, Vol 7, Iss 8, p e44171 (2012) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0044171⟩ |
| Popis: | International audience; Adrenal cortical carcinomas (ACC) are rare but aggressive tumours associated with poor prognosis. The two most frequent alterations in ACC in patients are overexpression of the growth factor IGF2 and constitutive activation of Wnt/β-catenin signalling. Using a transgenic mouse model, we have previously shown that constitutive active β-catenin is a bona fide adrenal oncogene. However, although all these mice developed benign adrenal hyperplasia, malignant progression was infrequent, suggesting that secondary genetic events were required for aggressive tumour development. In the present paper, we have tested IGF2 oncogenic properties by developing two distinct transgenic mouse models of Igf2 overexpression in the adrenal cortex. Our analysis shows that despite overexpression levels ranging from 7 (basal) to 87 (ACTH-induced) fold, Igf2 has no tumour initiating potential in the adrenal cortex. However, it induces aberrant accumulation of Gli1 and Pod1-positive progenitor cells, in a hedgehog-independent manner. We have also tested the hypothesis that Igf2 may cooperate with Wnt signalling by mating Igf2 overexpressing lines with mice that express constitutive active β-catenin in the adrenal cortex. We show that the combination of both alterations has no effect on tumour phenotype at stages when β-catenin-induced tumours are benign. However, there is a mild promoting effect at later stages, characterised by increased Weiss score and proliferation. Formation of malignant tumours is nonetheless a rare event, even when Igf2 expression is further increased by ACTH treatment. Altogether these experiments suggest that the growth factor IGF2 is a mild contributor to malignant adrenocortical tumourigenesis. |
| Databáze: | OpenAIRE |
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