Expression of targeting protein for xklp2 associated with both malignant transformation of respiratory epithelium and progression of squamous cell lung cancer.

Abstract

Purpose: Expression of targeting protein for Xklp2 (TPX2), a microtubule-associated protein, is tightly cell cycle regulated. Abnormally expressed TPX2 has been reported in various malignancies, but less is known in lung cancer. The present study appraised the significance of TPX2 aberrant expression for tumorigenesis and progression of human squamous cell carcinoma (SCC) in lung. Experimental Design and Results: The expressive status of TPX2 was firstly examined with lung cancer (L, PAa, and PG) and immortalized bronchial epithelial (C45, M-BE,Tr, and Y-BE) cell lines, and TPX2 expression was detected at both RNA and protein levels by reverse transcription-PCR andWestern blotting, respectively. Immunofluorescence staining on M-BE cells showed that the subcellular localization of TPX2 protein is in nucleus at interphase and mitotic spindle at metaphase. Immunohistochemical analyses were subsequently done on the precancerous lesions derived from 114 patients and the tumor tissues of 432 patients with SCC in lung. Extremely low levels of TPX2 protein were found in the normal bronchial epithelia and alveoli, whereas gradually increased TPX2 protein levels were observed in the squamous metaplasia, dysplasia, carcinoma in situ, and invasive tumor tissues. Statistical analysis showed that the TPX2 immunohistochemistry labeling index was correlated with the differentiation grade, stage, and lymphous metastasis of SCC in lung and that TPX2 overexpression is significantly associated with decreased 5-year survival rate of the patients. Conclusions: Aberrant expression of TPX2 may play important role(s) in both malignant transformation of respiratory epithelium and progression of squamous cell lung cancer and could serve as a prognostic predictor for the disease.

Overexpression of the receptor for hyaluronan-mediated motility, correlates with expression of microtubule-associated protein in human oral squamous cell carcinomas

“…TPX2 is a cell cycle-associated protein and plays a significant role in the microtubule formation at kinetochores (5), although its overexpression induces monopolar spindle structures in Xenopus egg extracts (25). Overexpression of TPX2 has been reported in several human cancers (22). In the present study, we found that the expression level of TPX2 mRNA was significantly increased in oral SCCs compared with normal gingivae.…”

“…The reaction mixture contained 1.0 μg of cDNA, 10 μl of SYBR-Green PCR master mix (Toyobo, Tokyo, Japan) and 10 pmol of each pair of oligonucleotide primers. Previously published primer sequences were used for RHAMM and TPX2 (12,22). The primer sequences were: RHAMM; 5'-CAGGTCACCCAAA GGAGTCTCG-3' (sense), 5'-CAAGCTCATCCAGTGTT TGC-3' (antisense) (537 bp PCR products), TPX2; 5'-ACCT TGCCCTACTAAGATT-3' (sense), 5'-AATGTGGCACAG GTTGAGC-3' (antisense) (176 bp PCR products), and G3PDH; 5'-ACCACAGTCCATGCCATCAC-3' (sense), 5'-TCCACCACCCTGTGGCTGTA-3' (antisense).…”

Phosphorylation of p53 Is Regulated by TPX2-Aurora A in Xenopus Oocytes

“…Polo-like kinase 1, MAPK, and Cdc2) are not affected is important for the following reasons. First, both Aurora A and TPX2 (initially identified as REPP86 (restrictedly expressed proliferation-associated protein of 86 kDa) are overexpressed in some tumors (61)(62)(63). Furthermore, knockdown of TPX2 significantly reduces the survival of multiple human cancer cell lines (64).…”

Cdh1 controls the stability of TACC3

“…30,41,42 Introduction of non-degradable mutant of NuSAP, TPX2 or Aurora B into cells resulted in disordered mitosis caused by abnormal spindle structure and/or promote anchorage-independent growth, similar to the phenotypes of these factors overexpressed in cancer tissues. 43,44 These findings strongly suggest that Cdh1-mediated degradation of mitotic spindle regulators is crucial for proper cell cycle progression. Thus, further identification of a non-degradable mutant of TACC3 should help to elucidate the regulatory event of Cdh1 on TACC3 in cell cycle progression.…”