Delta Np63 alpha mediates proliferation and apoptosis in human gastric cancer cells by the regulation of GATA-6

The oncogenic isoform of the p63 protein, Delta Np63 alpha, has been found to be overexpressed in numerous human squamous cell carcinomas. However, the role of Delta Np63 alpha in human gastric cancer remains unknown. To evaluate this role, we screened a panel of gastric cancer cell lines for Delta Np63 alpha expression and found that they are correlated with the differentiation status of the cell lines. Using the MKN28 gastric cancer cell line for loss-of-function or gain-of-function of Delta Np63 alpha in our experiments, we observed that forced expression of Delta Np63 alpha promoted cell proliferation as assessed by the MTT and colony formation assays, and increased the GATA-6 expression. In contrast, down-regulation of Delta Np63 alpha via small interfering RNA suppressed cell proliferation, induced cell apoptosis, and reduced the expression of GATA-6. In conclusion, our data suggest that Delta Np63 alpha plays an important role in cell growth and proliferation of gastric cancer cells, which may be associated with the regulation of GATA-6 expression. This is the first study exploring the biological functions and the underlying mechanism of Delta Np63 alpha during gastric cancer development. It also identifies potential targets for anti-tumor treatment.