Protein kinase CK2: Signaling and tumorigenesis in the mammary gland

摘要

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 rate 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 NFkB pathways and upregulation of c-Myc. CK2 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 IkB and thereby regulate basal NFkB levels; in the mammary cell lines and tumors, CK2 activity correlates with NFkB levels and inhibition of CK2 downregulates NFkB. 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.