Abstract. The targeting protein for the Xenopus kinesin-like protein 2 (TPX2), a microtubule-associated protein, has been utilized as a tool to evaluate, more precisely, the proliferative behavior of tumor cells. The abnormal expression of TPX2 in a variety of malignant tumor types has been reported, however less is known about its role in cervical cancer. In the present study, the association between TPX2 expression and the biological behavior of cervical cancer, was investigated. Immunohistochemistry and RT-PCR were used to detect the expression of TPX2 in cervical cancer tissues. The inhibitory effect of TPX2-siRNA on the growth of SiHa human cervical carcinoma cells was studied in vitro. TPX2 expression was identified as significantly higher in cervical carcinoma compared with the control, normal cervical tissues. TPX2 siRNA transfected into SiHa cells induced apoptosis and inhibited cell proliferation and invasion. Similar results were obtained by in vivo transplantation, as TPX2 siRNA transfection significantly reduced tumor growth of the xenograft in nude mice. The results demonstrated that TPX2 is important in the regulation of tumor growth in cervical cancer and therefore may be a potential therapeutic target as a novel treatment strategy.
IntroductionTargeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein. It is one of the best-known factors regulated by the RanGTP gradient and has a functional role in mitosis. The appearance and subsequent expression of TPX2 is mediated by the cell cycle, emerging at G1-S stage and diminishing following the completion of cytokinesis (1).In recent studies, it has been revealed that TPX2 is overexpressed in various carcinoma tissue types, including lung (2), breast (3) and salivary gland cancer (4). In this study, it was demonstrated that the overexpression of TPX2 in tumor cells caused exuberant amplification of the centrosome, developed aneuploidy and transformation, promotion of tumor proliferation and differentiation, as well as downregulation of tumor apoptosis (2-6). Conversely, it has also been demonstrated that inhibiting TPX2 and its associated pathways in tumor cells, leads to cancer cell apoptosis. This provides evidence that TPX2 may be a potential therapeutic candidate for the development of novel pharmacological cancer treatments (5,7,8).One recent study suggested that TPX2 may also be expressed in cervical carcinoma (8), however the exact function of TPX2 in cervical cancer formation and regulation remains elusive. In the present study, the expression of TPX2 in cervical carcinoma in human patients and the human cervical cancer cell line SiHa cells was examined. Gene-silencing methods were utilized to specifically knock-down TPX2 expression in vitro and in vivo, to advance the understanding of the regulatory mechanisms of TPX2 in cervical cancer development. Our results may provide invaluable experimental data, to facilitate in the diagnosis and treatment of cervical cancer in the future.
Materials and methodsClinic...