Nephroblastoma Overexpressed/Cysteine-Rich Protein 61/Connective Tissue Growth Factor/Nephroblastoma Overexpressed Gene-3 (NOV/CCN3), a Selective Adrenocortical Cell Proapoptotic Factor, Is Down-Regulated in Childhood Adrenocortical Tumors
| Autor: | Bonald C. Figueiredo, Giovanna Assis Rodrigues, Alina Nico West, Cécile Martinerie, Enzo Lalli, Maryvonne Laurent, J.-C. Mas, Malika Arhatte, Mabrouka Doghman, Hélène Thibout, Gerard P. Zambetti, A. Bongain, Patrick Auberger, Sébastien Grosso, Juliana de Moura |
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| Přispěvatelé: | Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Croissance, différenciation et processus tumoraux, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de la survie et de la mort cellulaire et infection virale, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Department of Biochemistry, St Jude Children's Research Hospital, Service de Pédiatrie, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Service de Gynécologie Ostétrique, Centro de Genética Molecular e Pesquisa do Câncer em Crianças (CEGEMPAC), Instituto de Pesquisa Pelé Pequeno Principe, Université Nice Sophia Antipolis (... - 2019) (UNS) |
| Rok vydání: | 2007 |
| Předmět: |
Steroidogenic factor 1
Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Fluorescent Antibody Technique Receptors Cytoplasmic and Nuclear Apoptosis Steroidogenic Factor 1 Biochemistry Tissue culture 0302 clinical medicine Endocrinology Adrenocortical carcinoma RNA Neoplasm Child Luciferases 0303 health sciences Reverse Transcriptase Polymerase Chain Reaction Adrenal cortex Flow Cytometry Adrenal Cortex Neoplasm Gene Expression Regulation Neoplastic medicine.anatomical_structure Caspases 030220 oncology & carcinogenesis Intercellular Signaling Peptides and Proteins Adenoma medicine.medical_specialty DNA Complementary Immunoblotting Down-Regulation Connective tissue [SDV.CAN]Life Sciences [q-bio]/Cancer Biology Transfection Immediate-Early Proteins Nephroblastoma Overexpressed Protein 03 medical and health sciences stomatognathic system Cell Line Tumor Internal medicine medicine Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology RNA Messenger 030304 developmental biology Homeodomain Proteins Growth factor Carcinoma Biochemistry (medical) Connective Tissue Growth Factor medicine.disease Adrenal Cortex Neoplasms Enzyme Activation Adrenal Cortex Adrenal Cortex Carcinoma Transcription Factors |
| Zdroj: | Journal of Clinical Endocrinology and Metabolism Journal of Clinical Endocrinology and Metabolism, 2007, 92 (8), pp.3253-60. ⟨10.1210/jc.2007-0342⟩ Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2007, 92 (8), pp.3253-60. ⟨10.1210/jc.2007-0342⟩ |
| ISSN: | 1945-7197 0021-972X |
| Popis: | CONTEXT: Childhood adrenocortical tumors (ACTs) have a fetal adrenal phenotype and overexpress steroidogenic factor-1 (SF-1). Nephroblastoma overexpressed (NOV)/cysteine-rich protein 61/connective tissue growth factor/nephroblastoma overexpressed gene-3 mRNA is significantly down-regulated in childhood ACTs. OBJECTIVE: The objective of the study was to measure NOV protein levels in childhood ACTs and characterize NOV expression regulation and biological function in human adrenocortical cells. DESIGN AND SETTING: Protein extracts from ACT and normal adrenal cortex samples, human adrenocortical carcinoma H295R, primary adrenocortical tumors and fetal adrenal cultures, tissue culture supernatants, and cell lysates from H295R cells overexpressing SF-1 in an inducible fashion were used. MAIN OUTCOME MEASURES: NOV protein levels were measured by enzyme-linked immunoassay and immunoblot. Transient transfection assays were used to study the activity of NOV promoter. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, caspase assays, and flow cytometry were used to assess the proapoptotic activity of NOV on cells in culture. RESULTS: NOV mRNA and protein expression is lower in childhood ACTs than in normal adrenal cortex. No significant difference was observed between adenomas and carcinomas. SF-1 overexpression down-regulates NOV at the transcriptional level. NOV has a selective proapoptotic activity toward human adrenocortical cells. The C-terminal domain of NOV is responsible for its proapoptotic effect. NOV protein is expressed in DAX-1-positive human fetal adrenal cells. CONCLUSIONS: NOV is a selective proapoptotic factor for human adrenocortical cells. Reduced expression of NOV in ACTs may play an important role in the process of childhood ACT tumorigenesis, accounting at least in part for the defect of apoptotic regression of the fetal adrenal that has been proposed to be responsible for tumor formation. |
| Databáze: | OpenAIRE |
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