Protein kinase CK2: signaling and tumorigenesis in the mammary gland
Autor: | E, Landesman-Bollag, D H, Song, R, Romieu-Mourez, D J, Sussman, R D, Cardiff, G E, Sonenshein, D C, Seldin |
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Rok vydání: | 2002 |
Předmět: |
DNA
Complementary Time Factors Transcription Genetic Blotting Western Down-Regulation Breast Neoplasms Mammary Neoplasms Animal Mice Transgenic Adenocarcinoma Protein Serine-Threonine Kinases Gene Expression Regulation Enzymologic Proto-Oncogene Proteins c-myc Mice Genes Reporter Proto-Oncogene Proteins Animals Humans Apigenin Phosphorylation Casein Kinase II Flavonoids Dose-Response Relationship Drug NF-kappa B Neoplasms Experimental Zebrafish Proteins Immunohistochemistry Precipitin Tests Rats Up-Regulation Gene Expression Regulation Neoplastic Wnt Proteins Signal Transduction |
Zdroj: | Molecular and cellular biochemistry. 227(1-2) |
ISSN: | 0300-8177 |
Popis: | 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 CK2alpha 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 NFkappaB pathways and upregulation of c-Myc. CK2 is capable of phosphorylating the key signaling molecule in the Wnt pathway, the transcriptional cofactor beta-catenin, and regulating its turnover. CK2 is known to phosphorylate IkappaB and thereby regulate basal NFkappaB levels; in the mammary cell lines and tumors, CK2 activity correlates with NFkappaB levels and inhibition of CK2 downregulates NFkappaB. 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. |
Databáze: | OpenAIRE |
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