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Published on: October 27, 2014
Disabled-2 and Axin are concurrently colocalized and underexpressed in lung cancers
Hong-Tao Xu1, Lian-He Yang, Qing-Chang Li
1Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang 110001, China. xu.htao@yahoo.com.cn
Abstract:
Disabled-2 expression is reduced in many cancers, suggesting that it is a potential tumor suppressor protein. To elucidate the role of Disabled-2 in lung cancer, we examined the expression of Disabled-2, the Disabled-2-binding protein Axin, and DNA methyltransferase-1 in lung cancer tissues and corresponding normal lung tissues using immunohistochemistry and Western blots. We also determined the subcellular localization of Axin and Disabled-2 in A549 cells using confocal immunofluorescence. Disabled-2 expression was significantly reduced in lung cancers and was colocalized and coexpressed with Axin (correlation coefficient = 0.321, P < .001 for cytoplasmic expression; correlation coefficient = 0.393, P < .001 for nuclear expression). Reduced nuclear Disabled-2 expression was correlated with the differentiation (P = .048) and TNM stage (P = .048) of the tumor. The cytoplasmic expression of Axin was also correlated with differentiation (P = .042), whereas the nuclear expression of Axin was correlated with both histologic type (P = .001) and TNM stage (P < .001) of lung cancers. Expression of DNA methyltransferase-1 was negatively correlated with the cytoplasmic expression of Axin (correlation coefficient = -0.244, P = .012) but positively correlated with the histologic type (P = .004), differentiation (P = .036), TNM stage (P = .044), and lymphatic metastasis (P = .011). Expressions of Disabled-2 and Axin were concurrently reduced and correlated with the malignant phenotype of lung cancers. Enhanced expression of DNA methyltransferase-1 correlated with the reduced expression of Axin and could be a marker for lung cancer development and progression.
Insights
Disabled-2, a potential tumor suppressor, is reduced in lung cancer. Its reduced expression, along with Axin, correlates with tumor malignancy, while increased DNA methyltransferase-1 indicates progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Disabled-2 is implicated as a tumor suppressor due to its reduced expression in various cancers.
- Understanding the role of Disabled-2 in lung cancer pathogenesis is crucial for identifying potential therapeutic targets.
Purpose of the Study:
- To investigate the expression patterns of Disabled-2, Axin, and DNA methyltransferase-1 in lung cancer.
- To determine the correlation between these proteins and clinicopathological features of lung cancer.
- To elucidate the subcellular localization of Disabled-2 and Axin in lung cancer cells.
Main Methods:
- Immunohistochemistry and Western blot analysis were used to assess protein expression in lung cancer tissues and normal lung tissues.
- Confocal immunofluorescence microscopy was employed to determine the subcellular localization of Axin and Disabled-2 in A549 lung cancer cells.
- Statistical analysis, including correlation coefficients and P-values, was used to evaluate relationships between protein expression and clinicopathological parameters.
Main Results:
- Disabled-2 expression was significantly reduced in lung cancers compared to normal tissues.
- Reduced Disabled-2 and Axin expression was concurrently observed and correlated with the malignant phenotype of lung cancers.
- Increased DNA methyltransferase-1 expression was positively correlated with tumor progression, including histologic type, differentiation, TNM stage, and lymphatic metastasis, and negatively correlated with cytoplasmic Axin expression.
Conclusions:
- Disabled-2 and Axin expression are concurrently reduced in lung cancer and are associated with tumor malignancy.
- Reduced nuclear Disabled-2 expression correlates with poor tumor differentiation and advanced TNM stage.
- Elevated DNA methyltransferase-1 expression is linked to reduced Axin expression and may serve as a biomarker for lung cancer development and progression.
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