Protein kinase CK2 in mammary gland tumorigenesis

Protein kinase CK2 is a ubiquitous and evolutionarily conserved serine/thre onine kinase that is upregulated in many human cancers and can serve as an oncogene in lymphocytes. Recently, we have demonstrated that CK2 potentiate s Wnt/beta -catenin signaling in mammary epithelial cells. To determine whe ther CK2 overexpression contributes to mammary tumorigenesis, we have perfo rmed comparative studies of human and rat breast cancer specimens and we ha ve engineered transgenic mice with dysregulated expression of CK2 alpha in the mammary gland. We find that CK2 is highly expressed in human breast tum or specimens and in carcinogen-induced rat mammary tumors. Overexpression o f CK2 alpha in the mammary gland of transgenic mice, under control of the M MTV-LTR, causes hyperplasia and dysplasia of the female mammary gland. Thir ty per cent of the female MMTV-CK2 alpha transgenic mice develop mammary ad enocarcinomas at a median of 23 months of age, often associated with Wnt pa thway activation, as evidenced by upregulation of beta -catenin protein, NF -kappaB activation and upregulation of c-Myc also occur frequently. Thus, i n mice, rats, and humans, dysregulated expression of CK2 is associated with and is capable of contributing to mammary tumorigenesis, Targeted inhibiti on of CK2 could be useful in the treatment of breast cancer.