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

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 expressio...

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Bibliographic Details
Published in:Clinical cancer research 2006-02, Vol.12 (4), p.1121-1127
Main Authors: Ma, Ying, Lin, Dongmei, Sun, Wenyue, Xiao, Ting, Yuan, Jinsong, Han, Naijun, Guo, Suping, Feng, Xiaoli, Su, Kai, Mao, Yousheng, Cheng, Shujun, Gao, Yanning
Format: Article
Language:English
Subjects:
Blotting, Western
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
Cell Cycle Proteins - analysis
Cell Cycle Proteins - genetics
Cell Line, Tumor
Cell Transformation, Neoplastic
Disease Progression
Epithelium - metabolism
Epithelium - pathology
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Microtubule-Associated Proteins - analysis
Microtubule-Associated Proteins - genetics
Neoplasm Proteins - analysis
Neoplasm Proteins - genetics
Nuclear Proteins - analysis
Nuclear Proteins - genetics
Phosphoproteins - analysis
Phosphoproteins - genetics
Prognosis
Respiratory Mucosa - metabolism
Respiratory Mucosa - pathology
Reverse Transcriptase Polymerase Chain Reaction
RNA, Neoplasm - genetics
RNA, Neoplasm - metabolism
Survival Analysis
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Summary: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 and Western 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.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-05-1766