The
transcription factor GATA3 is known as a
breast tumor suppressor as well as a urothelial marker, and its loss is often seen in high-grade invasive
bladder cancer. Nonetheless, GATA3 functions in
bladder cancer cells remain largely unknown. In this study, we assessed the effects of GATA3 silencing via RNA interference on cell migration, invasion, and proliferation of
bladder cancer. GATA3 expression was downregulated in all four
bladder cancer lines examined, compared with a non-neoplastic urothelial line SVHUC. Knockdown of GATA3 in the
bladder cancer lines (5637, TCC-SUP, J82) resulted in promotion of cell migration and invasion as well as increases in the expression of their related molecules, such as
vascular endothelial growth factor,
matrix metalloproteinase (MMP)-2, and MMP-9, and the activity of MMP-2 and MMP-9. GATA3 loss was also associated with an increasing level of a mesenchymal marker
N-cadherin and a decreasing level of an epithelial marker β-
catenin. Consistent with these findings, enforced expression of GATA3 in UMUC3 inhibited cell migration and invasion. However, GATA3 showed marginal effects on
bladder cancer cell viability and the expression of cell cycle- or apoptosis-related molecules. Additionally, in contrast to
bladder cancer lines, no significant effects of GATA3 silencing on cell migration were seen in SVHUC. These findings suggest that GATA3 plays an important role in the prevention of
bladder cancer progression and
metastasis by inhibiting cell migration and invasion as well as epithelial-to-mesenchymal transition.