Human growth-differentiation factor 3 (hGDF3) : developmental regulation in human teratocarcinoma cell lines and expression in primary testicular germ cell tumours

• Published in: Oncogene Vol. 16; no. 1; pp. 95 - 103
• Main Authors: CARICASOLE, A. A. D, VAN SCHAIK, R. H. N, DE BRUIJN, D, KRAMER, P, DE JONG, F. H, VAN DEN EIJNDEN-VAN RAAIJ, A. J. M, ZEINSTRA, L. M, WIERIKX, C. D. J, VAN GURP, R. J. H. L. M, VAN DEN POL, M, LOOIJENGA, L. H. J, OOSTERHUIS, J. W, PERA, M. F, WARD, A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 08.01.1998
• Subjects: Activins; Amino Acid Sequence; Base Sequence; Biological and medical sciences; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; DNA Fragmentation; DNA, Complementary; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental - drug effects; Growth Differentiation Factor 3; Growth Substances - genetics; Humans; Inhibins - pharmacology; Intercellular Signaling Peptides and Proteins; Male; Molecular and cellular biology; Molecular Sequence Data; RNA, Messenger - genetics; Sequence Homology, Amino Acid; Teratoma - genetics; Teratoma - pathology; Testicular Neoplasms - genetics; Testicular Neoplasms - pathology; Tretinoin - pharmacology; Tumor Cells, Cultured; Genetic mapping; Human; Nucleotide sequence; Transforming growth factor β; Homology; Chromosome C12; Malignant tumor; Germinal cell; Cell differentiation; Gene expression; Testicle; Malignant teratoma; Regulation(control); Cell line; Gene; Tumor; Male genital diseases; Testicular diseases
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1201515

We describe the cloning and initial characterization of a novel cDNA from human embryonal carcinoma (EC) cells. This cDNA, which we named human growth differentiation factor 3 (hGDF3), encodes the homologue of mouse GDF3, a TGFbeta superfamily member belonging to the Growth/Differentiation Factors. We have analysed the expression of hGDF3 in human embryonal carcinoma cell lines and in primary testicular germ cell tumours of adolescents and adults (TGCTs). Expression of hGDF3 in human EC cell lines is stem cell-specific, is down-regulated upon RA-mediated differentiation and is increased upon culture of the cells in the presence of activin A. In TGCTs, hGDF3 expression is low in seminomas, while expression in non-seminomas is readily detectable and appears to be associated with the EC and yolk sac components in the tumours. We have also mapped the hGDF3 locus to the short arm of human chromosome 12, a region consistently overrepresented in human testicular germ cell tumours. Thus, hGDF3 represents an embryonal carcinoma stem cell-associated marker both in vitro and in vivo.