Loss of GATA3 in bladder cancer promotes cell migration and invasion.
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.
Department of Pathology and Laboratory Medicine; University of Rochester Medical Center; Rochester, NY USA; Department of Urology; 2nd Affiliated Hospital; Zhejiang University School of Medicine; Hangzhou, PR China.
Yi
Y
Li
Department of Pathology and Laboratory Medicine; University of Rochester Medical Center; Rochester, NY USA; Departments of Pathology and Urology; Johns hopkins University school of Medicine; Baltimore, MD UsA.
Hitoshi
H
Ishiguro
Department of Pathology and Laboratory Medicine; University of Rochester Medical Center; Rochester, NY USA; Departments of Pathology and Urology; Johns hopkins University school of Medicine; Baltimore, MD UsA.
Takashi
T
Kawahara
Departments of Pathology and Urology; Johns hopkins University school of Medicine; Baltimore, MD UsA.
Eiji
E
Kashiwagi
Department of Pathology and Laboratory Medicine; University of Rochester Medical Center; Rochester, NY USA.
Koji
K
Izumi
Department of Pathology and Laboratory Medicine; University of Rochester Medical Center; Rochester, NY USA; Departments of Pathology and Urology; Johns hopkins University school of Medicine; Baltimore, MD UsA.
Hiroshi
H
Miyamoto
D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D050990:GATA3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
D050990:GATA3 Transcription Factor
GATA3; bladder cancer; cell invasion; cell migration; cell proliferation