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. 2010 Sep 7;103(6):852-60.
doi: 10.1038/sj.bjc.6605835. Epub 2010 Aug 24.

Expression of parvin-beta is a prognostic factor for patients with urothelial cell carcinoma of the upper urinary tract

C-F Wu  1 , K-F Ng, C-S Chen, P-L Chang, C-K Chuang, W-H Weng, S-K Liao, S-T Pang
Affiliations

Expression of parvin-beta is a prognostic factor for patients with urothelial cell carcinoma of the upper urinary tract

C-F Wu et al. Br J Cancer. .

Abstract

Background: Parvin-beta (ParvB), a potential tumour suppressor gene, is a focal adhesion protein. We evaluated the role of ParvB in the upper urinary tract urothelial cell carcinoma (UUT-UC).

Methods: ParvB mRNA and proteins levels in UUT-UC tissue were investigated by quantitative real-time polymerase chain reaction and western blot analysis, respectively. In addition, the expression of ParvB in tissues from patients with UUT-UC at different stages was evaluated by immunohistochemistry. Furthermore, biological functions of ParvB in urothelial cancer cells were investigated using a doxycycline-inducible overexpression system and siRNA.

Results: Western blot and mRNA analysis showed downregulation of ParvB expression in frozen UUT-UC tissue. Immunohistochemistry revealed high staining intensity of ParvB in normal urothelium, which decreased markedly at advanced stages of UUT-UC (P=0.0000). Moreover, ParvB was an independent prognostic indicator for disease-specific survival of patients with UUT-UC. Functional assays indicated that overexpression of ParvB in an urothelial cancer cell line resulted in decreased cell growth rate and ability to migrate. In contrast, knockdown of ParvB expression increased cell migration ability.

Conclusions: Downregulation of ParvB expression significantly increased urothelial cancer cell growth and migration. Downexpression of ParvB level in UUT-UC correlated with tumour stage, and was an independent unfavourable prognostic factor for disease-specific survival of patients with UUT-UC.

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Figures

Figure 1
Figure 1
The study of ParvB mRNA (A) and protein level (B) in human upper urinary tract urothelial carcinoma in paired samples indicated that ParvB was downregulated in tumour sample as compared with normal tissue. Error bars indicate standard deviation for triplicate experiment data (□: normal urothelium; ▪: tumour).
Figure 2
Figure 2
A DOX-inducible ParvB cell line was created and the expression of inducible ParvB is dependent on the concentration of doxycycline (A-1) and in a time-dependent pattern (A-2). (B) Overexpression of ParvB significantly decreased cell growth rate (P=0.012) and (C) inhibit the migration ability of the tumour cell as shown by the matrigel assay (P=0.001) (□: WT DOX− ▪: WT DOX+ ▵: Dox− ▴: Dox+)
Figure 3
Figure 3
(A-1 and -2) ParvB was successfully knocked down using siRNA in urothelial carcinoma cell line. (B) The knockdown of ParvB did not affect tumour cell growth rate, but (C) did significantly promote cell migration (P=0.000) (□: WT; △: Ctrl; ▴: shRNA-6).
Figure 4
Figure 4
Examples of immunohistochemical staining intensity of ParvB in upper urinary tract urothelium cell carcinoma: (A) strong, (B) moderate, (C) weak and (D) absent.
Figure 5
Figure 5
Kaplan–Meier estimation of disease-specific survival of patient with primary upper urinary tract urothelium cell carcinoma against: (A) tumour grade (P=0.0121); (B) pT stage (P=0.0000); (C) tumour size (P=0.0002); (D) tumour vascular invasion (P=0.0000); (E) ParvB staining intensity (P=0.0000); and (F) disease-specific 5-year survival curve.
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