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Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
The interrelationships between Src, Cav-1 and RhoGD12 in transitional cell carcinoma of the bladder
1Institute of Cancer, College of MVLS, University of Glasgow, Western Infirmary, Glasgow G11 6NT, UK.
Background:
The aim of this current study was to assess the expression and activity of Src family kinases, focal adhesion kinase (FAK), caveolin (Cav-1) and RhoGD12 in bladder cancer.
Methods:
Fifty-eight patients with a new diagnosis of bladder cancer undergoing transurethral resection were included. Immunohistochemical staining was utilised to assess expression of c-Src, dephosphorylated (SrcY(530)), phosphorylated Src (Y(419)), phosphorylated FAK (FAK Y(861)), Cav-1 and RhoGD12. Expression was assessed using the weighted histoscore method.
Results:
High expression of dephosphorylated Y(527), phosphorylated Y(416) and phosphorylated FAK Y(861) in the membrane were associated with increased cancer-specific survival (P=0. 01, P=0.001, P=0.008, respectively) and expression of Y(416) in the membrane was an independent factor on multivariate analysis when combined with known clinical parameters (P=0.008, HR 0.288, 95% CI 0.11-0.72).
Conclusion:
These results demonstrate that in contrast to other solid tumours, activation of the Src family members and downstream signalling proteins are associated with a good prognosis in transitional cell carcinoma of the bladder, and activated Src has a positive relationship with RhoGD12.
Insights
Activated Src family kinases and downstream proteins indicate a good prognosis in bladder cancer, unlike other tumors. This activation positively correlates with RhoGD12 expression, suggesting a favorable outcome for patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Investigating signaling pathways in bladder cancer is crucial for understanding tumor progression.
- Src family kinases (SFKs), focal adhesion kinase (FAK), caveolin-1 (Cav-1), and RhoGD12 are implicated in various cancers.
Purpose of the Study:
- To evaluate the expression and activity of SFKs, FAK, Cav-1, and RhoGD12 in bladder cancer patients.
- To determine the prognostic significance of these molecules in transitional cell carcinoma of the bladder.
Main Methods:
- Immunohistochemical staining was performed on tumor samples from 58 bladder cancer patients.
- Expression levels of c-Src, phosphorylated Src (Y419), dephosphorylated Src (Y527), phosphorylated FAK (Y861), Cav-1, and RhoGD12 were quantified using the weighted histoscore method.
Main Results:
- High membrane expression of dephosphorylated Src (Y527) and phosphorylated Src (Y419) correlated with increased cancer-specific survival.
- Elevated phosphorylated FAK (Y861) at the membrane also showed association with better survival.
- Membrane Src Y419 expression was an independent prognostic factor in multivariate analysis.
Conclusions:
- Contrary to findings in other solid tumors, activated SFKs and downstream signaling proteins are associated with a favorable prognosis in bladder cancer.
- Activated Src demonstrates a positive relationship with RhoGD12 expression, suggesting a potential interplay in bladder tumor biology.
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