TPX 2 in human clear cell renal carcinoma : Expression , function and prognostic significance

Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein. TPX2 is considered to be an important gene in tumorigenesis; however, the particular function of TPX2 in the development of human renal cell carcinoma (RCC) is unknown. In the present study, the expression, function and prognostic significance of TPX2 in human RCC was analyzed. A total of 286 tissue samples from patients with RCC who had undergone nephrectomies were utilized. Subsequently, the expression of TPX2 protein was investigated using immunohistochemistry and western blotting, and TPX2 mRNA expression was examined using reverse transcription-quantitative polymerase chain reaction. To establish the effect of TPX2 on the proliferation and invasion of the RCC cells, TPX2 expression was increased by stable transfection with a TPX2 vector and TPX2 expression was decreased using small interfering RNA. Proliferation of the RCC cells was analyzed using a WST-1 assay and an animal xenograft model with BALB/c nude mice, whilst invasion of the RCC cells was examined using a Matrigel-coated invasion chamber. It was demonstrated that TPX2 expression was significantly higher in the RCC tissues compared with normal kidney tissues (P<0.05). Furthermore, TPX2 expression was associated with tumor size, histological grade and tumor stage (P<0.05), and was observed to markedly increase the proliferation and invasion of the RCC cells. It may be concluded that the expression of TPX2 is significantly upregulated in RCC tissue, subsequently increasing the proliferative and invasive ability of RCC cells. Therefore, the protein may serve as a therapeutic target and independent prognostic factor in the treatment of human RCC. Introduction Human renal cell carcinoma (RCC) is the most lethal urinary malignancy and consists of a number of different pathological types, including clear cell, chromophobe and papillary RCC, which all arise from the epithelium of the renal tubules (1,2). The most prevalent RCC subtype is clear cell, accounting for 85% of all RCC cases (3). Generally, RCC is resistant to conventional radiotherapy and chemotherapy (4,5). Prognosis for patients with metastatic RCC is poor, with a median survival time of 8 months and a 5-year survival rate of 10% (6). Although certain genes have been investigated as potential prognostic predictors and therapeutic targets for RCC, the molecular mechanisms underlying the development and progression of RCC remain largely unknown. Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein, and functions to regulate the construction of the mitotic spindle by promoting microtubule nucleation from chromatin and stabilization of the spindle microtubules (7,8). It has been demonstrated that TPX2 overexpression induces the amplification of centrosomes and results in DNA polyploidy (9). TPX2 also serves a crucial role in the proliferation of various tumor cells (10,11). TPX2 expression is closely regulated by the cell cycle, and exhibits particularly high expression in proliferating cells transitioning between the G1 and S phase (12-14). Certain studies have demonstrated that the TPX2 gene, in addition to elevated gene copy numbers, is frequently identified in various human malignancies, including lung carcinoma (15), salivary gland cancer (16), esophageal cell carcinoma (17) and breast cancer (18). Furthermore, the upregulated expression of TPX2 has been observed in a number of different tumors, including bladder and colon cancer (19,20). Such results have revealed the correlation between TPX2 and the tumorigenesis of cancer. In addition, it has been demonstrated that the overexpression of TPX2 serves an important role in the progression and invasion of human malignancies (21), and that its expression is associated with the aggressiveness of ovarian cancer (22). Previous studies have reported that TPX2 is involved in cell proliferation and associated with poor prognosis in patients with esophageal cell carcinoma (23,24), supporting the hypothesis that TPX2 functions as a tumor promoter in this particular type of cancer. When combined, the aforementioned reports suggest that TPX2 may be involved in the progression of malignant tumors; however, the function of TPX2 expression in human RCC TPX2 in human clear cell renal carcinoma: Expression, function and prognostic significance QI CHEN, BIN CAO, NING NAN, YU WANG, XU ZHAI, YOUFANG LI and TIE CHONG Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China Received December 4, 2014; Accepted January 15, 2016 DOI: 10.3892/ol.2016. 4396 Correspondence to: Dr Tie Chong, Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, Shaanxi 710004, P.R. China E-mail: tiechong898@163.com