JWA deficiency induces malignant transformation of murine embryonic fibroblast cells.

Abstract

The present study aimed to investigate the effects of JWA knockout (JWA-/-) on malignant transformation of murine embryonic fibroblast (MEF) cells using a conditional JWA-/- mouse model. Once MEF cells were prepared, the potential role of JWA-/- on proliferation, migration, invasion and colony formation of MEF cells was investigated by cytological examination. The effects of JWA-/- on the regulation and protein expression levels of epithelial-mesenchymal transition (EMT)-related proteins in MEF cells, including poly(ADP-ribose) polymerase-1 (PARP-1), vimentin, β-catenin and E-cadherin, were investigated using western blot analysis. The tumorigenicity of JWA deficiency was explored using nude mouse xenografts and subcutaneous inoculation of MEF cells exhibiting JWA-/-. JWA-/- was able to increase cell proliferation, migration, invasion and colony formation in the malignant transformation of MEF cells. The protein expression levels of PARP-1, vimentin and β-catenin were upregulated, whereas E-cadherin was downregulated in JWA-/- MEF cells. The tumor formation was observed in mice following subcutaneous inoculation of MEF with JWA-/-, whereas no tumor was formed in the mice treated with functional JWA MEF cells. In conclusion, the present findings suggest that JWA-/- has important roles in cell proliferation, migration, invasion and colony formation and is able to induce the malignant transformation of MEF cells. The expression levels of EMT-related proteins changed and tumorigenicity increased in JWA-/- MEF cells compared with cells with functional JWA. The present findings indicate that JWA may function as an anti-oncogene in tumorigenesis.