Regulatory role of nucleophosmin during the differentiation of human liver cancer cells.
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.
Department of Hepatic Biliary Pancreatic Vascular Surgery, the First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China.
Dong-Hui
DH
Xu
Medical College of Xiamen University, Xiamen, Fujian 361102, P.R. China.
Fan
F
Liu
School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, P.R. China.
Xiao
X
Li
School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, P.R. China.
Xiang-Feng
XF
Chen
School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, P.R. China.
Guang-Jun
GJ
Jing
School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, P.R. China.
Fu-Yun
FY
Wu
Medical College of Xiamen University, Xiamen, Fujian 361102, P.R. China.
Song-Lin
SL
Shi
Medical College of Xiamen University, Xiamen, Fujian 361102, P.R. China.
Qi-Fu
QF
Li
D000081:Acetamides / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D000090243:Nucleophosmin
D000081:Acetamides; D000970:Antineoplastic Agents; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C014026:hexamethylene bisacetamide