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Purpose: Axis inhibition (Axin) is an important negative regulator of the Wnt pathway. This study investigated the relationship between Axin expression and sensitivity to X-rays in non-small-cell lung cancer (NSCLC) to find a useful indicator of radiosensitivity. Methods and Materials: Tissue from NSCLC patients, A549 cells, and BE1 cells expressing Axin were exposed to 1-Gy of X-radiation. Axin and p53 expression levels were detected by immunohistochemistry and reverse transcription-PCR. Apoptosis was determined by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay and FACS (fluorescence-activate cell sorter) analysis. Caspase-3 activity was determined by Western blotting. Phospho-JNK expression was determined by immunofluorescence. Results: The expression of Axin was significantly lower in NSCLC tissues than in normal lung tissues (p less than 0.05). Axin expression correlates with differentiation, TNM staging, and lymph node metastasis of NSCLC (p less than 0.05). Its expression negatively correlates with the expression of p53(mt) (p=0.000) and positively correlates with apoptosis (p=0.002). The prognosis of patients with high expression of Axin was better than those with low expression. X-radiation increases Axin expression in NSCLC tissue, and caspase-3 is significantly higher in samples in which Axin is increased (p less than 0.05). Both X-radiation and Axin induce apoptosis of A549 and BE1 cells; however, the combination of the two enhances the apoptotic effect (p less than 0.05). In A549 cells, inhibition of p53 blocks Axin-induced apoptosis, whereas in BE1 cells, the JNK pathway is required. Conclusions: Axin induces the p53 apoptotic pathway in cells where this pathway is intact; however, in cells expressing p53(mt), Axin induces apoptosis via the JNK pathway. Elevated Axin expression following X-ray exposure is a reliable indicator for determining the radiosensitivity of NSCLC.

The aim of this study was to investigate the relationship between the expression of p120ctn in human lung squamous cell carcinoma, adenocarcinoma and its clinicopathologic significance. The expression of p120ctn in tumors and adjacent normal lung tissues from 143 patients was examined by immunohistochemistry and Western blot. Expression of p120ctn occurs mainly in the cell membrane of normal bronchial mucosa. Abnormal expression of p120ctn, including cytoplasmic and reduced membranous expression, was found in 114 of 143 specimens (79.7%) and was significantly associated with poor differentiation, high TNM stage, and lymph node metastasis (P<0.05 for each) but not with histologic subtype. The Kaplan-Meier survival test revealed that abnormal expression of p120ctn was related to poor survival (P<0.001). A Cox regression analysis revealed that abnormal p120ctn expression was an independent factor in predicting patient survival (P=0.024). Compared with that in normal lung tissues, membranous protein level was lower in tumors (P=0.003). Abnormal expression of p120ctn is associated with tumor progression and poor prognosis in lung squamous cell carcinoma and adenocarcinoma. Reduced expression or even the absence of p120ctn isoform 1 and 3 in tumor cell membranes may be responsible for the abnormal expression of p120ctn that has been found in lung cancer.