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

Wu CF, Ng KF, Chen CS, Chang PL, Chuang CK, Weng WH, Liao SK, Pang ST - Br. J. Cancer (2010)

Bottom Line: 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.Downregulation of ParvB expression significantly increased urothelial cancer cell growth and migration.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Division of Urology, Chia-Yi Chang Gung Memorial Hospital, Chia-Yi, Taiwan.

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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Examples of immunohistochemical staining intensity of ParvB in upper urinary tract urothelium cell carcinoma: (A) strong, (B) moderate, (C) weak and (D) absent.
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fig4: Examples of immunohistochemical staining intensity of ParvB in upper urinary tract urothelium cell carcinoma: (A) strong, (B) moderate, (C) weak and (D) absent.

Mentions: To determine whether ParvB is a prognostic factor in patients with UUT-UC, immunohistochemical analysis of paraffin-embedded UUT-UC specimens was performed. The relationships between ParvB expression and clinical demographic characteristics of patients with UUT-UC are shown in Table 1. Immunohistochemistry revealed ParvB expression in the cytoplasm of UC cells. Comparison of ParvB expression levels revealed downregulation in UC specimens relative to normal urothelium, with the lowest level of ParvB expression in muscle invasive tumours relative to non-muscle invasive tumour (Figure 4). Moreover, this study also showed a strong negative correlation for staining intensity in relation to pT stage, tumour grade and tumour size (Table 1). In contrast, vascular invasive property, which significantly influences prognosis in patients with UUT-UC, did not correlate with ParvB expression (Table 1). We further investigated whether ParvB expression can be used as an independent prognostic factor. According to Kaplan–Meier analysis with the log-rank test, tumour grade, pT stage, tumour size, vascular invasion and downexpression of ParvB level were unfavourable factors for disease-specific survival of patients with UUT-UC (Figure 5). The disease-specific 5-year survival rate is 76%. Furthermore, Cox hazard regression analysis showed that pT stage, ParvB expression and vascular invasion were independent unfavourable factors for disease-free survival of patients with UUT-UC (Table 2).


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

Wu CF, Ng KF, Chen CS, Chang PL, Chuang CK, Weng WH, Liao SK, Pang ST - Br. J. Cancer (2010)

Examples of immunohistochemical staining intensity of ParvB in upper urinary tract urothelium cell carcinoma: (A) strong, (B) moderate, (C) weak and (D) absent.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2966628&req=5

fig4: Examples of immunohistochemical staining intensity of ParvB in upper urinary tract urothelium cell carcinoma: (A) strong, (B) moderate, (C) weak and (D) absent.
Mentions: To determine whether ParvB is a prognostic factor in patients with UUT-UC, immunohistochemical analysis of paraffin-embedded UUT-UC specimens was performed. The relationships between ParvB expression and clinical demographic characteristics of patients with UUT-UC are shown in Table 1. Immunohistochemistry revealed ParvB expression in the cytoplasm of UC cells. Comparison of ParvB expression levels revealed downregulation in UC specimens relative to normal urothelium, with the lowest level of ParvB expression in muscle invasive tumours relative to non-muscle invasive tumour (Figure 4). Moreover, this study also showed a strong negative correlation for staining intensity in relation to pT stage, tumour grade and tumour size (Table 1). In contrast, vascular invasive property, which significantly influences prognosis in patients with UUT-UC, did not correlate with ParvB expression (Table 1). We further investigated whether ParvB expression can be used as an independent prognostic factor. According to Kaplan–Meier analysis with the log-rank test, tumour grade, pT stage, tumour size, vascular invasion and downexpression of ParvB level were unfavourable factors for disease-specific survival of patients with UUT-UC (Figure 5). The disease-specific 5-year survival rate is 76%. Furthermore, Cox hazard regression analysis showed that pT stage, ParvB expression and vascular invasion were independent unfavourable factors for disease-free survival of patients with UUT-UC (Table 2).

Bottom Line: 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.Downregulation of ParvB expression significantly increased urothelial cancer cell growth and migration.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Division of Urology, Chia-Yi Chang Gung Memorial Hospital, Chia-Yi, Taiwan.

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.

Show MeSH
Related in: MedlinePlus