1. TPX2 overexpression in medullary thyroid carcinoma mediates TT cell proliferation.
- Author
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Yang X, Liu G, Xiao H, Yu F, Xiang X, Lu Y, Li W, Liu X, Li S, and Shi Y
- Subjects
- Adult, Apoptosis, Aurora Kinase A genetics, Blotting, Western, Carcinoma, Medullary genetics, Carcinoma, Medullary metabolism, Cell Cycle Checkpoints, Cell Cycle Proteins antagonists & inhibitors, Cell Cycle Proteins genetics, Cyclin B1 genetics, Female, Flow Cytometry, Gene Expression Regulation, Neoplastic, Humans, Immunoenzyme Techniques, Lymphatic Metastasis, Male, Microtubule-Associated Proteins antagonists & inhibitors, Microtubule-Associated Proteins genetics, Nuclear Proteins antagonists & inhibitors, Nuclear Proteins genetics, RNA, Messenger genetics, RNA, Small Interfering genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Thyroid Neoplasms genetics, Thyroid Neoplasms metabolism, Tumor Cells, Cultured, Aurora Kinase A metabolism, Carcinoma, Medullary secondary, Cell Cycle Proteins metabolism, Cell Proliferation, Cyclin B1 metabolism, Microtubule-Associated Proteins metabolism, Nuclear Proteins metabolism, Thyroid Neoplasms pathology
- Abstract
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.
- Published
- 2014
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