蛋白激酶 D 同工型：浸润性乳腺癌治疗的新靶点？
Protein kinase D isoforms: new targets for therapy in invasive breast cancers?
出版信息
Expert Rev Anticancer Ther. 2013 Aug;13(8):895-8. doi: 10.1586/14737140.2013.816460. Epub 2013 Aug 14.
Abstract
The Protein Kinase D (PKD) family of serine/threonine kinases consists of three members-PKD1, PKD2, and PKD3. While PKD1 in many cancers has been identified as a suppressor of the invasive phenotype, the two other PKD subtypes, PKD2 and PKD3, have been attributed oncogenic functions. In invasive Breast Cancer cells PKD1 expression is downregulated by methylation of the promoter. On the other hand, PKD2 and PKD3 are not silenced, and drive proliferation, invasion, and mediate chemoresistance. Two strategies emerge to utilize this knowledge for novel treatment opportunities. First, pan PKD inhibitors could be developed and used for these aggressive cancers. An alternative approach to obtain similar effects would be to induce the re-expression of PKD1.
摘要
蛋白激酶 D（PKD）家族的丝氨酸/苏氨酸激酶由三个成员组成-PKD1、PKD2 和 PKD3。虽然许多癌症中的 PKD1 已被确定为侵袭表型的抑制剂，但另外两种 PKD 亚型 PKD2 和 PKD3 则被赋予了致癌功能。在侵袭性乳腺癌细胞中，PKD1 的表达通过启动子的甲基化而被下调。另一方面，PKD2 和 PKD3 没有被沉默，并且驱动增殖、侵袭并介导化学抗性。出现了两种策略来利用这一知识为新的治疗机会。首先，可以开发泛 PKD 抑制剂并将其用于这些侵袭性癌症。另一种获得类似效果的方法是诱导 PKD1 的重新表达。
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