TPX2 overexpression in medullary thyroid carcinoma mediates TT cell proliferation.
TPX2 (targeting protein for xenopus kinesin-like protein 2), a microtubule-associated protein, plays an important role in the formation of the mitotic spindle. Abnormal expression of TPX2 in various types of malignant tumors has been reported, but less is known for medullary thyroid cancer (MTC). We investigated the expression of TPX2 in human MTC tissues and its potential use as a therapeutic target. Immunohistochemical analysis of TPX2 expression was performed for 32 cases of MTC and 8 cases of normal thyroid. TPX2 expression was found to be significantly higher in MTC compared to normal thyroid tissues (P < 0.05), and to be associated with tumor size, lymph node metastasis, and advanced disease stage. The cellular effects of TPX2 knockdown, including cell proliferation, apoptosis, cell cycle diffusions, and mitotic gene expression were investigated using small interfering RNA (siRNA). TPX2-siRNA caused G1 and G2-phase cell cycle arrest, inhibited cell proliferation, and induced apoptosis. TPX2-siRNA also downregulated Aurora-A and cyclinB1 protein expression in MTC cells and enhanced the expression of p53 protein (P < 0.05). These results suggest that TPX2 may be of potential use as a new marker for MTC prognosis and therapy.
Department of Endocrinology (Section I), Tangshan Workers Hospital, Tangshan, China.
Xiaolin
X
Yang
Geling
G
Liu
Hongzhen
H
Xiao
Fang
F
Yu
Xiuxiu
X
Xiang
Yifang
Y
Lu
Weijuan
W
Li
Xiuling
X
Liu
Sha
S
Li
Yanping
Y
Shi
D000328:Adult; D017209:Apoptosis; D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D018276:Carcinoma, Medullary / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
C534699:CCNB1 protein, human; D018797:Cell Cycle Proteins; D056744:Cyclin B1; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C122167:TPX2 protein, human; D064096:Aurora Kinase A