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DLK1: increased expression in gliomas and associated with oncogenic activities

Abstract

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.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

GBM:

glioblastoma multiforme

T98G/w, U87/w, and U118/w:

wild-type GBM cell lines (T98G, U87, and U118)

T98G/neo, U87/neo, and U118/neo:

T98G, U87, U118 cells transfected with neo-containing vector

T98G/D, U87/D, and U118/D:

T98G, U87, U118 cells stably transfected with the DLK1 expression vector

FACS:

fluorescence-activated cell sorting

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Acknowledgements

This work was supported in part by National Institutes of Health, Cindy and Alan Horn Fund, Inger Fund, Parker Hughes Trust, NSFC30470980, and a grant from the Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center. HPK is a member of the Molecular Biology Institute and Jonsson Comprehensive Cancer Center at UCLA, and holds the endowed Mark Goodson Chair of Oncology Research at Cedars-Sinai Medical Center/UCLA School of Medicine.

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Yin, D., Xie, D., Sakajiri, S. et al. DLK1: increased expression in gliomas and associated with oncogenic activities. Oncogene 25, 1852–1861 (2006). https://doi.org/10.1038/sj.onc.1209219

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