Research Center for Women's Disease, Department of Life Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
FEBS Lett. 2011 Mar 9;585(5):755-60. doi: 10.1016/j.febslet.2011.01.018. Epub 2011 Jan 18.
The cancerous inhibitor of protein phosphatase 2A (CIP2A) increases the migration and metastasis of various cancer cells. Overexpression of CIP2A has been shown to increase the proliferation of MDA-MB-231 cells. We thus assessed whether CIP2A expression is associated with sensitivity to doxorubicin. MDA-MB-231 cells showed an increase in CIP2A expression after treatment with doxorubicin, while MCF-7 cells showed a decrease in CIP2A expression. The overexpression of CIP2A in MCF-7 cells overcame the inhibition of cell proliferation in response to doxorubicin treatment. CIP2A expression was not affected by wild-type or mutant p53. However, mutant p53 blocked doxorubicin-mediated CIP2A down-regulation in HCT116 cells. As a regulation mechanism of doxorubicin-mediated CIP2A expression, we showed that phosphorylated Akt was involved in the suppression of CIP2A expression.
癌蛋白磷酸酶 2A 的抑制剂 CIP2A（cancerous inhibitor of protein phosphatase 2A）可促进多种癌细胞的迁移和转移。已有研究表明，CIP2A 的过表达可促进 MDA-MB-231 细胞的增殖。因此，我们评估了 CIP2A 的表达是否与多柔比星的敏感性相关。多柔比星处理后 MDA-MB-231 细胞的 CIP2A 表达增加，而 MCF-7 细胞的 CIP2A 表达减少。在 MCF-7 细胞中过表达 CIP2A 可克服多柔比星处理引起的细胞增殖抑制。野生型或突变型 p53 均不影响 CIP2A 的表达。然而，突变型 p53 可阻断 HCT116 细胞中多柔比星介导的 CIP2A 下调。作为多柔比星介导的 CIP2A 表达的调控机制，我们表明磷酸化 Akt 参与了 CIP2A 表达的抑制。
