Protein kinase CK2: Signaling and tumorigenesis in the mammary gland
Protein kinase CK2: Signaling and tumorigenesis in the mammary gland
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DOI：
10.1023/a:1013108822847
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发表时间：
2001-01-01
影响因子：
4.3
通讯作者：
Seldin, DC
中科院分区：
文献类型：
--
作者：
Landesman-Bollag, E;Song, DH;Seldin, DC
乳腺癌是女性癌症死亡的主要原因，导致这种常见散发性疾病的基因异常仍在积极调查中。据报道，CK2在人类乳腺癌中表达上调，这些研究证实了这一点；CK2在大鼠致癌物诱导的乳腺癌中也表达上调。在乳腺中过度表达CK2α的转基因小鼠会发生乳腺增生、异型增生，最终导致腺癌，这表明CK2的异常表达可以促进乳腺上皮的转化。这些乳腺肿瘤有证据表明Wnt和NF-kappaB通路被激活，c-Myc上调。CK2能够磷酸化Wnt途径中的关键信号分子-转录辅助因子β-连环蛋白，并调节其周转。已知CK2可磷酸化I kappaB，从而调节基础的核因子kappaB水平；在乳腺细胞系和肿瘤中，CK2活性与核因子kappaB水平相关，抑制CK2可下调核因子kappaB。因此，CK2可能通过调控乳腺上皮细胞转录调控的关键途径促进乳腺癌的发生，抑制CK2在乳腺癌和其他癌症的治疗中具有潜在的作用。
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 CK2 alpha 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 NF kappaB 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 I kappaB and thereby regulate basal NF kappaB levels; in the mammary cell lines and tumors, CK2 activity correlates with NF kappaB levels and inhibition of CK2 downregulates NF kappaB. 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.