DLK1: increased expression in gliomas and associated with oncogenic activities

• Published in: Oncogene Vol. 25; no. 13; pp. 1852 - 1861
• Main Authors: YIN, D, XIE, D, SAKAJIRI, S, MILLER, C. W, ZHU, H, POPOVICIU, M. L, SAID, J. W, BLACK, K. L, KOEFFLER, H. P
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 23-03-2006; Nature Publishing Group
• Subjects: Biological and medical sciences; Blotting, Western; Brain cancer; Brain Neoplasms - genetics; Brain Neoplasms - physiopathology; Brain tumors; Cell cycle; Cell growth; Cell lines; Cell Movement; Cell physiology; Cell Proliferation; Cell surface; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Neoplastic - genetics; Cloning; Contact inhibition; Cyclin D1; Disease Progression; DNA, Complementary - biosynthesis; Embryogenesis; Epidermal growth factor; Explants; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Glioblastoma; Glioma; Glioma - genetics; Glioma - physiopathology; Hematology; Humans; Intercellular Signaling Peptides and Proteins; Medical sciences; Medicine; Membrane Proteins - biosynthesis; Molecular and cellular biology; Neuroendocrine tumors; Neurology; Oncology; Preadipocyte factor 1; Proteins; Repressor Proteins - biosynthesis; Transfection; Tumor Cells, Cultured; Tumors of the nervous system. Phacomatoses; Los Angeles California; United States > US; Nervous system diseases; expression; Glioma; DLK 1; Central nervous system disease; Tumor; Gene expression; Carcinogenesis; oncogenic activities
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1209219

DLK1 (delta-like) is a transmembrane and secreted protein in the epidermal growth factor-like homeotic family. Although expressed widely during embryonic development, only a few tissues retain the expression in adults. Neuroendocrine tumors often highly express this protein; therefore, we hypothesized that brain tumors might also express it. This study found that the expression of DLK1 in gliomas was higher than that in normal brain (P < 0.05). After stable transfection of a DLK1 cDNA expression vector into GBM cell lines, their proliferation was increased. Furthermore, they lost contact inhibition, had enhanced anchorage-independent growth in soft agar, and had significantly greater capacity to migrate. Western blot studies showed that expression of cyclin D1, CDK2, and E2F4 were increased, and Rb levels were decreased in these cells. DLK1 was found on the cell surface and secreted in the medium from the transfected GBM cells. DLK1-enriched condition medium stimulated the growth of glioblastoma multiforme cell lines and explants. DLK1 antibody blocked cell growth stimulated by DLK1. In summary, these results suggest that DLK1 may play a role in the formation or progression of gliomas.