JWA regulates N-methyl-N'-nitro-N-nitrosoguanidine induced malignant transformation in human bronchial epithelial cells

Abstract

To investigate the role and possible mechanism of JWA in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) inducing human bronchial epithelial (HBE) cells' neoplastic transformation. JWA overexpression vector and its stable transfection HBE cells were established. The characteristics of transformed HBE cells were determined by methyl thiazolyl tetrazolium (MTT) assay and the soft agar colony formation assay. The expressions of JWA and P53 were detected by Western blot. The growth rates of the HBE cells which were treated with MNNG were significantly accelerated than the JWA overexpression HBE cells and controlled HBE cells (P < 0.05). The soft agar colony formation of JWA overexpression HBE cells with and without MNNG treatment (8.06% and 10.14%) was significantly lower than that of the normal HBE cells with MNNG treatment (26.80%) (P < 0.01). After exposure of MNNG, the P53 expressions were gradually increased in HBE cells with the increased passages. However, the expression of P53 in JWA over expressed HBE cells showed a different manner. P53 reached an over expression peak at early stage (the first passage), and then with a gradually down-regulated expression spectrum with increased passages of the cells. JWA might be a key molecule and play an important role in MNNG inducing neoplastic transformation in HBE cells through regulation of the expression of P53.