Regulatory role of nucleophosmin during the differentiation of human liver cancer cells.
Regulatory role of nucleophosmin during the differentiation of human liver cancer cells.
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DOI：
10.3892/ijo.2014.2407
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发表时间：
2014-07
影响因子：
5.2
通讯作者：
Dong-hui Xu;Fan Liu;Xiao Li;Xiang-Feng Chen;Guang-Jun Jing;Fu-Yun Wu;Song-Lin Shi;Qi-Fu Li
中科院分区：
文献类型：
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作者：
Dong-hui Xu;Fan Liu;Xiao Li;Xiang-Feng Chen;Guang-Jun Jing;Fu-Yun Wu;Song-Lin Shi;Qi-Fu Li
核磷蛋白（Nucleophosmin，NPM，B23）主要定位于细胞核，在结肠癌、卵巢癌、前列腺癌和胃癌等多种肿瘤中表达。在HMBA诱导人肝癌细胞分化过程中筛选差异核基质蛋白的同时鉴定了NPM。本研究通过检测NPM在临床肝癌组织和肝癌细胞系中的异常表达和亚细胞定位，为进一步揭示NPM在肝癌细胞增殖和分化中的作用提供依据。此外，我们还研究了NPM与几种重要蛋白质之间的潜在相互作用。我们的研究结果表明，NPM蛋白在癌细胞中过表达，这与癌组织中的mRNA相对于相应的非癌组织的过表达一致。我们还发现用分化试剂HMBA处理后，NPM的蛋白质和mRNA水平降低。我们关注的是新公共管理的异常定位。免疫组化和免疫荧光显示NPM在肝癌组织中异常定位于胞浆和核浆，在SMMC-7721细胞系中与c-Myc、c-Fos、P53和Rb共定位。通过GST pull-down和免疫共沉淀实验证实了NPM与上述蛋白的相互作用。这些结果表明，NPM在肝癌中起着调节作用，值得深入研究。
Nucleophosmin (NPM, also known as B23), mainly localized in the nucleolus, has been reported to be overexpressed in many types of human cancer, including colon, ovarian, prostate and gastric cancer. NPM was identified while screening the differential nuclear matrix proteins during HMBA-induced differentiation of human liver cancer cells. We investigated the aberrant expression and subcellular localization of NPM in clinical liver cancer tissues and a cell line with the aim of providing more evidence for revealing the roles of NPM on regulating liver cancer cell proliferation and differentiation. In addition, we studied the potential interaction between NPM and several important proteins. Our results revealed that NPM protein was overexpressed in cancer cells, which was in accordance with the overexpressed mRNA in cancer tissues compared to the corresponding non-cancer tissues. We also found a decrease of NPM in protein and mRNA levels upon treatment with the differentiation reagent HMBA. We focused on the aberrant localization of NPM. Immunochemistry and immunofluorescence revealed aberrant cytoplasmic and nucleoplasm localization of NPM in liver cancer tissues and its colocalization with c-Myc, c-Fos, P53 and Rb in the SMMC-7721 cell line. The interactions between NPM and the above proteins were confirmed by GST pull-down assay and co-immunoprecipitation assay. These findings indicate that NPM plays a regulatory role in liver cancer, which deserves in-depth investigation.