1. Specific detection of type II human chorionic gonadotropin beta subunit produced by trophoblastic and neoplastic cells
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A. Nordor, F. Troalen, L. Aldaz-Carroll, Virginie Dangles-Marie, Thierry Fournier, Melanie Cocquebert, A.-M. Hersant, Alain Pecking, B. Guery, Dominique Bellet, Sophie Richon, D. Stevens, Jean Guibourdenche, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Centre de recherche de l'Institut Curie [Paris], Institut Curie [Paris], Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut Gustave Roussy (IGR), Génétique (Biologie pathologie), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpital René HUGUENIN (Saint-Cloud), Hôpital Renée Sabran [CHU - HCL], Hospices Civils de Lyon (HCL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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), and ORANGE, Colette
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[SDV]Life Sciences [q-bio] ,Clinical Biochemistry ,Biochemistry ,Human chorionic gonadotropin ,0302 clinical medicine ,Pregnancy ,Neoplasms ,Gene expression ,Chorionic Gonadotropin, beta Subunit, Human ,TRANSCRIPTION ,reproductive and urinary physiology ,Immunoassay ,0303 health sciences ,General Medicine ,Immunohistochemistry ,CANCER ,3. Good health ,Trophoblasts ,[SDV] Life Sciences [q-bio] ,PROGNOSTIC VALUE ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,embryonic structures ,Female ,hormones, hormone substitutes, and hormone antagonists ,EXPRESSION ,endocrine system ,GENES ,medicine.drug_class ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,Monoclonal antibody ,03 medical and health sciences ,Syncytiotrophoblast ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Placenta ,Cell Line, Tumor ,medicine ,Humans ,ASSAYS ,FAMILIAL HCG SYNDROME ,030304 developmental biology ,Biochemistry, medical ,Biochemistry (medical) ,Trophoblast ,Molecular biology ,EVOLUTION ,ALPHA ,MRNA Sequencing ,Down Syndrome ,MONOCLONAL-ANTIBODIES ,Gonadotropins - Abstract
International audience; Background: The sequence of the beta-subunit of human chorionic gonadotropin (hCG beta varies depending on whether hCG beta is encoded by type I or type II genes. Type II genes are upregulated in trophoblast and cancer but hCG beta can be detected in the serum of nonpregnant women and healthy individuals. We aimed to determine whether monoclonal antibody (mAb) FBT11-II specifically detects hCG beta encoded by type II genes (type II hCG beta). Methods: Competitive inhibition assays with synthetic peptides, immunocytochemical and immunohistochemical studies, type II hCG beta dosing immunoassays and sequencing of CGB genes were performed. Results: Competitive inhibition assays determined that mAb FBT11-II recognizes the type II hCG beta derived peptide. CGB mRNA sequencing of JEG-3 (trophoblastic) and 124 (bladder) cell lines confirmed that JEG-3 expresses type II genes while T24 expresses exclusively type I. FBT11-II only recognizes JEG-expressed hCG beta. Placenta immunohistochemical studies confirmed that type II hCG beta expression is restricted to the syncytiotrophoblast. Immunoassays detected type II hCG beta in serum of patients with either nontrophoblastic cancers or fetal Down syndrome. Conclusion: Type II gene expression can be detected using FBT11-II. This specific recognition could improve the clinical usefulness of assays aimed at either managing aggressive tumors or screening for Down syndrome.
- Published
- 2015
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