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DNA-PK, the DNA-activated protein kinase, is differentially expressed in normal and malignant human tissues

Oncogene volume 18, pages 3114–3126 (1999)Cite this article

Abstract

DNA-PK is a nuclear, serine/threonine protein kinase required for repairing DNA double-strand breaks and for V(D)J recombination. To determine the distribution of DNA-PK in human tissues, we assayed paraffin-embedded sections of normal and cancerous tissues for DNA-PKcs and Ku80 by immunohistochemistry. We also assayed for Brca2, a human tumor suppressor gene that is implicated in the repair of DNA strand-breaks. Brca2 was strongly expressed in epithelial cells of the breast, endometrium, and thymus, in tingible body macrophages of follicular germinal centers of lymphoid tissue, and in reticuloendothelial cells in the spleen. DNA-PKcs and Ku80 expression was usually parallel, but both were expressed in a highly cell- and tissue-specific manner. The highest levels were observed in spermatogenic cells (but not in spermatozoa), and in neurons and glial cells of the central and autonomic nervous system. Neither protein was consistently expressed in liver nor in resting mammary epithelium, but lactating breast epithelium was strongly positive for DNA-PKcs and Ku80. In contrast to established human cell cultures, expression between cells in the same tissue was highly selective in the epidermis, exocrine pancreas, renal glomeruli, the red pulp of the spleen, and within cellular compartments of tonsils, lymph nodes, and thymus. Most cancerous tissues were consistently positive for DNA-PKcs and Ku80, except invasive carcinoma of the breast. DNA-PKcs, Ku80, and Ku70 mRNAs were expressed in all normal tissues with relatively little variation in levels. Our results suggest that the apparent absence of DNA-PKcs and Ku80 from some cells or tissues is a consequence of post-transcriptional mechanisms that regulate protein levels.

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Acknowledgements

We thank S Lamb and N Marchenko for excellent technical assistance, D Colflesh, Microscopy Imaging Center, State University of New York at Stony Brook, for assistance with computer graphics, and D Hill, Oncogene Research Products for providing antisera to Brca2 and for helpful discussions. This work was supported by US Public Health Service grant GM52825 to CW Anderson, and grant #4318 from the Council for Tobacco Research and #MRMC BC971469 from the US Army to U Moll. CW Anderson is supported in part by the Office of Health and Environmental Research of the US Department of Energy.

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  1. Malini M Gupta

    Present address: Nastech Pharmaceutical Company Inc., 45 Davids Drive, Hauppauge, 11788, New York, USA

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  1. Department of Pathology, State University of New York at Stony Brook, Stony Brook, New York, 11794, USA

    Ute Moll & Raymond Lau

  2. Biology Department, 50 Bell Avenue, Brookhaven National Laboratory, Upton, 11973, New York, USA

    Michael A Sypes, Malini M Gupta & Carl W Anderson

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Moll, U., Lau, R., Sypes, M. et al. DNA-PK, the DNA-activated protein kinase, is differentially expressed in normal and malignant human tissues. Oncogene 18, 3114–3126 (1999). https://doi.org/10.1038/sj.onc.1202640

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