Aberrant hypermethylation and reduced expression of disabled-2 promote the development of lung cancers

  • Authors:
    • Xue-Mei Xie
    • Zi-Yin Zhang
    • Lian-He Yang
    • Da-Lei Yang
    • Na Tang
    • Huan‑Yu Zhao
    • Hong-Tao Xu
    • Qing-Chang Li
    • En-Hua Wang
  • View Affiliations

  • Published online on: August 29, 2013     https://doi.org/10.3892/ijo.2013.2084
  • Pages: 1636-1642
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Abstract

Disabled-2 (Dab2) is considered a tumor suppressor and is downregulated in cancers. We examined the promoter methylation status and expression levels of Dab2, and investigated their roles in the development of lung cancers. Methylation-specific PCR was employed to analyze the methylation status of Dab2 in 100 lung cancer tissues. The cytoplasmic and nuclear expression of the Dab2 protein was determined using western blot analysis. Demethylation treatment using 5-Aza-2-deoxycytidine (5-Aza-dC) was performed in three lung cancer cell lines. Dab2 expression was upregulated by Dab2 transfection or interrupted by Dab2 siRNA in lung cancer cells. Proliferative and invasive ability tests were performed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTS) and a Matrigel invasion assay, respectively. The methylation rate of Dab2 was significantly higher in lung cancer tissues compared to normal lung tissues. Dab2 methylation correlated with the reduced nuclear and cytoplasmic expression of Dab2, as well as the TNM stage and lymphatic metastasis of lung cancers. Treatment with 5-Aza-dC was able to eliminate the hypermethylation of Dab2, enhance Dab2 expression, and inhibit β-catenin expression, and the proliferative and invasive ability of lung cancer cells. Upregulation of Dab2 expression reduced β-catenin expression and proliferation and invasiveness of lung cancer cells. However, interruption of Dab2 expression induced the opposite results. Dab2 methylation is common in lung cancers, and is one of the most important factors responsible for the reduced expression of Dab2. Aberrant hypermethylation and reduced expression of Dab2 promote the development of lung cancers.
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November 2013
Volume 43 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Xie, X., Zhang, Z., Yang, L., Yang, D., Tang, N., Zhao, H. ... Wang, E. (2013). Aberrant hypermethylation and reduced expression of disabled-2 promote the development of lung cancers. International Journal of Oncology, 43, 1636-1642. https://doi.org/10.3892/ijo.2013.2084
MLA
Xie, X., Zhang, Z., Yang, L., Yang, D., Tang, N., Zhao, H., Xu, H., Li, Q., Wang, E."Aberrant hypermethylation and reduced expression of disabled-2 promote the development of lung cancers". International Journal of Oncology 43.5 (2013): 1636-1642.
Chicago
Xie, X., Zhang, Z., Yang, L., Yang, D., Tang, N., Zhao, H., Xu, H., Li, Q., Wang, E."Aberrant hypermethylation and reduced expression of disabled-2 promote the development of lung cancers". International Journal of Oncology 43, no. 5 (2013): 1636-1642. https://doi.org/10.3892/ijo.2013.2084