ABSTRACT
Metastatic tumor antigen 2 (MTA2) is a member of the MTA family that is closely associated with tumor progression and metastasis. In this study, the expression profile of MTA2 in 223 cases of non-small cell lung cancer (NSCLC) tissues and two lung cancer cell lines was investigated. Interestingly, we found MTA2, which was believed to have nuclear distribution only, was distributed in both nucleus and cytoplasm in normal and cancer cells. Nuclear MTA2 expression was detected in 148 cases of NSCLC (66.4%), and was correlated with advanced TNM stages (p=0.023), tumor size (p=0.036), and lymph node metastasis (p=0.004). Besides, the Ki-67 proliferation index was significantly higher in nuclear MTA2-positive tumors than in nuclear MTA2-negative tumors (r=0.538, p=0.006). However, there was no significant difference in cytoplasmic MTA2 status by age, gender, tumor stage, histology, grade, lymph node metastasis, and Ki-67 proliferation index. Univariate analysis revealed nuclear MTA2 expression was correlated with poor overall survival (p=0.035), whereas there was a nonsignificant trend in the same direction for cytoplasmic MTA2 (p=0.134). Multivariate Cox regression analysis revealed the overexpression of nuclear and cytoplasmic MTA2 not to be independent factors predictive of poor disease outcome. Our data suggested that MTA2 might play roles in both the nucleus and cytoplasm in the progression of NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Histone Deacetylases/biosynthesis , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Repressor Proteins/biosynthesis , Adult , Aged , Carcinoma, Non-Small-Cell Lung/genetics , Cell Growth Processes/physiology , Cell Line, Tumor , Cell Nucleus/metabolism , Cytoplasm/metabolism , Histone Deacetylases/genetics , Humans , Immunohistochemistry , Lung Neoplasms/genetics , Middle Aged , Repressor Proteins/genetics , Retrospective StudiesABSTRACT
OBJECTIVE: To investigate the expression of p120(ctn) in non-small cell lung cancer (NSCLC) and its correlation with the clinical and pathologic parameters. METHODS: Immunohistochemistry (S-P method) was used to detect the expression of p120(ctn) in 143 NSCLC cases. The variation of protein expression was further analyzed in 36 cases by Western blot. The correlation with clinical and pathologic parameters was studied. RESULTS: Immunohistochemically, normal bronchial cells showed membranous expression for p120(ctn), while NSCLC was characterized by cytoplasmic or diminished membranous staining. The rate of abnormal p120(ctn) expression was 79.7% (114/143). There was a significant correlation between abnormal expression of p120(ctn) and tumor differentiation, clinical stage, lymph node metastasis and poor prognosis (< 0.05), but not histologic typing. Western blot showed that the total amount of p120(ctn) in normal bronchial cells was significantly higher than that in NSCLC. The p120(ctn) isoform 1 (120,000) and isoform 3 (100,000) were expressed in normal lung tissue, while there was a reduced expression or absence of isoform 1 in NSCLC. CONCLUSION: The expression of p120(ctn) is abnormal in NSCLC; p120(ctn) may serve as a useful prognostic marker for NSCLC.
