Protein kinase CK2 in mammary gland tumorigenesis

被引:256
作者
Landesman-Bollag, E
Romieu-Mourez, R
Song, DH
Sonenshein, GE
Cardiff, RD
Seldin, DC
机构
[1] Boston Med Ctr, Dept Med, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA
[3] Boston Univ, Dept Chem, Boston, MA 02118 USA
[4] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA
[5] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA
[6] Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA
关键词
casein kinase II; CK2; transgenic mice; breast cancer; NF-kappa B; beta-catenin;
D O I
10.1038/sj.onc.1204411
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein kinase CK2 is a ubiquitous and evolutionarily conserved serine/threonine kinase that is upregulated in many human cancers and can serve as an oncogene in lymphocytes. Recently, we have demonstrated that CK2 potentiates Wnt/beta -catenin signaling in mammary epithelial cells. To determine whether CK2 overexpression contributes to mammary tumorigenesis, we have performed comparative studies of human and rat breast cancer specimens and we have engineered transgenic mice with dysregulated expression of CK2 alpha in the mammary gland. We find that CK2 is highly expressed in human breast tumor specimens and in carcinogen-induced rat mammary tumors. Overexpression of CK2 alpha in the mammary gland of transgenic mice, under control of the MMTV-LTR, causes hyperplasia and dysplasia of the female mammary gland. Thirty per cent of the female MMTV-CK2 alpha transgenic mice develop mammary adenocarcinomas at a median of 23 months of age, often associated with Wnt pathway activation, as evidenced by upregulation of beta -catenin protein, NF-kappaB activation and upregulation of c-Myc also occur frequently. Thus, in mice, rats, and humans, dysregulated expression of CK2 is associated with and is capable of contributing to mammary tumorigenesis, Targeted inhibition of CK2 could be useful in the treatment of breast cancer.
引用
收藏
页码:3247 / 3257
页数:11
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