Yan Liang, Li Shenglei, Xu Changbao, Zhao Xinghua, Hao Bin, Li Huixiang, Qiao Baoping
Department of Urology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, Henan, 450052, China.
Tumour Biol. 2013 Dec;34(6):4089-100. doi: 10.1007/s13277-013-1000-z. Epub 2013 Jul 20.
Increasing evidence demonstrated that TPX2 was highly expressed and tightly associated with human tumor development and progression. However, its precise role in bladder carcinoma remains to be delineated. In the present study, we revealed the high expression of TPX2 at both mRNA and protein levels in bladder carcinoma tissues and cells, and TPX2 levels in pN1-3 and pT2-4 status were significantly higher than those in pN0 and pTa-T1 status, respectively. Additionally, high TPX2 level was strongly associated with pT status (P = 0.001), higher histological grade (P = 0.001), lymph node metastasis (P = 0.022), and shorter survival time (P = 0.0279). Further investigation showed that TPX2 level in T24 cells was markedly higher than those in 5637, J82 and RT4 cells, in which RT4, a well-differentiated cell line derived from bladder carcinoma with low-grade non-invasive T0, displayed the lowest TPX2 mRNA and protein levels. Besides, TPX2 overexpression promoted proliferation and tumorigenicity, shortened cell cycle in G0/G1 phase, and suppressed cell apoptosis in T24 cells; conversely, TPX2 depletion exhibited opposite effects. Furthermore, TPX2 overexpression evoked the elevation of cyclin D1 and cdk2 levels as well as reduction of p21 level and caspase-3 activity, whereas reversed effects were observed in TPX2-depleted T24 cells. Taken altogether, TPX2 may play a central role in the development and progression of bladder carcinoma, and thus inhibition of TPX2 level may be a novel strategy for therapy of the patients with bladder carcinoma.
越来越多的证据表明，TPX2高表达且与人类肿瘤的发生和进展密切相关。然而，其在膀胱癌中的具体作用仍有待阐明。在本研究中，我们发现TPX2在膀胱癌组织和细胞中的mRNA和蛋白质水平均高表达，且pN1-3和pT2-4状态下的TPX2水平分别显著高于pN0和pTa-T1状态下的水平。此外，TPX2高表达与pT状态（P = 0.001）、更高的组织学分级（P = 0.001）、淋巴结转移（P = 0.022）及较短的生存时间（P = 0.0279）密切相关。进一步研究表明，T24细胞中的TPX2水平明显高于5637、J82和RT4细胞，其中RT4是一种源自低级别非侵袭性T0期膀胱癌的高分化细胞系，其TPX2 mRNA和蛋白质水平最低。此外，TPX2过表达促进T24细胞增殖和致瘤性，缩短G0/G1期细胞周期，并抑制细胞凋亡；相反，TPX2缺失则产生相反的效果。此外，TPX2过表达导致细胞周期蛋白D1和cdk2水平升高以及p21水平和半胱天冬酶-3活性降低，而在TPX2缺失的T24细胞中观察到相反的效果。综上所述，TPX2可能在膀胱癌的发生和进展中起核心作用，因此抑制TPX2水平可能是治疗膀胱癌患者的一种新策略。
