Wnt4 overexpression promotes thymoma development through a JNK-mediated planar cell polarity-like pathway.

Abstract

Thymoma is the most common neoplasm of the anterosuperior mediastinum. Activation of the Wnt signaling pathway has a role in a variety of human cancers. The present objective was to examine c-Jun N-terminal kinase (JNK) mRNA and protein expression in thymoma cells undergoing apoptosis subsequent to downregulation of Wnt4. Wnt4 and JNK mRNA and protein expression was analyzed by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively, in 15 thymoma tissues and 6 thymus cyst tissues. Thymoma cells were cultured and transfected with shRNA plasmids targeting the Wnt4 gene. Wnt4 and JNK protein expression was detected by western blot analysis. Apoptosis was analyzed using Wright-Giemsa staining, Hoechst-33342/propidium iodine double staining and flow cytometry. The results showed that Wnt4 and JNK mRNA and protein expression were significantly increased in thymoma compared with normal thymus tissue. Subsequent to transfection, thymoma Wnt4 and JNK mRNA and protein expression were significantly decreased in shRNA-treated groups, with the strongest inhibition being 52.37%. Characteristic apoptotic morphological changes were observed and apoptosis increased. Overall, the present concluded that Wnt4 has an important role in thymoma development, which appears to be activated through a JNK mediated planar cell polarity-like pathway.