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Protein kinase CK2: Signaling and tumorigenesis in the mammary gland

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Abstract

Breast cancer is a major cause of cancer death in women, and the genetic abnormalities leading to the common sporadic forms of the disease are still under active investigation. CK2 has been reported to be upregulated in human breast cancer, which these studies confirm; CK2 is also upregulated in rat carcinogen-induced breast tumors. Transgenic mice overexpressing CK2α in the mammary gland develop mammary hyperplasia, dysplasia, and eventually adenocarcinomas, demonstrating that dysregulated expression of CK2 can contribute to transformation of the mammary epithelium. These mammary tumors have evidence of activation of the Wnt and NFκB pathways and upregulation of c-Myc. CK2 is capable of phosphorylating the key signaling molecule in the Wnt pathway, the transcriptional cofactor β-catenin, and regulating its turnover. CK2 is known to phosphorylate IκB and thereby regulate basal NFκB levels; in the mammary cell lines and tumors, CK2 activity correlates with NFκB levels and inhibition of CK2 downregulates NFκB. Thus, CK2 may promote breast cancer through dysregulation of key pathways of transcriptional control in the mammary epithelium, and inhibition of CK2 has a potential role in the treatment of breast and other cancers.

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Authors and Affiliations

  1. Department of Pathology, Boston University School of Medicine, Boston, MA, USA

    Esther Landesman-Bollag

  2. Department of Chemistry, Boston University, Boston, MA, USA

    Diane H. Song

  3. Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA

    Raphaelle Romieu-Mourez & Gail E. Sonenshein

  4. Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, College Park, MD, USA

    Daniel J. Sussman

  5. Center for Comparative Medicine, U.C. Davis School of Medicine, Davis, CA, USA

    Robert D. Cardiff

  6. Departments of Medicine and Microbiology, Boston University School of Medicine, EBRC4, 650 Albany Street, Boston, MA, 02118, USA

    David C. Seldin

Authors
  1. Esther Landesman-Bollag
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  2. Diane H. Song
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  3. Raphaelle Romieu-Mourez
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  4. Daniel J. Sussman
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  5. Robert D. Cardiff
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  6. Gail E. Sonenshein
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  7. David C. Seldin
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Correspondence to David C. Seldin.

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Landesman-Bollag, E., Song, D.H., Romieu-Mourez, R. et al. Protein kinase CK2: Signaling and tumorigenesis in the mammary gland. Mol Cell Biochem 227, 153–165 (2001). https://doi.org/10.1023/A:1013108822847

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