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[Expression and significance of FGFR2IIIc in chemoresistant bladder cancer cells]
Yule Chen1, Linlin Zhang2, Kaijie Wu2
1Department of Urology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China.
Objective:
To investigate the role of fibroblast growth factor receptor-2 (FGFR2) splice variant FGFR2IIIc in the regulation of mesenchymal-epithelial transition (MET) in doxorubicin-resistant bladder cancer cells.
Methods:
A doxorubicin-resistant human bladder cell line (253J/DOX) was generated from the bladder cancer cell line 253J by being continuously exposed to gradually increasing doses of doxorubicin. Chemosensitivity to doxorubicin was determined by MTT assay. The expressions of P-glycoprotein and FGFR2IIIc were evaluated by Western blotting and real-time RT-PCR, respectively. Changes in E-cadherin and vimentin were detected by Western blot analysis. Migration ability of 253J and 253J/DOX cells was analyzed by in vitro wound healing assay.
Results:
The resistant cells, 253J/DOX, were more resistant to doxorubicin than the parent cells. Western blotting and RT-PCR analysis indicated the higher levels of P-glycoprotein and FGFR2IIIc in 253J/DOX cells (P<0.05). Additionally, compared with the 253J cells, 253J/DOX cells presented the upregulation of E-cadherin, the downregulation of vimentin and the inhibition of migration ability.
Conclusion:
FGFR2IIIc-induced MET in chemoresistant bladder cancer cells may play an important role in the formation of metastatic lesions.
Insights
Fibroblast growth factor receptor-2 (FGFR2) splice variant FGFR2IIIc promotes mesenchymal-epithelial transition (MET) in doxorubicin-resistant bladder cancer cells. This process may contribute to the development of metastatic lesions in chemoresistant bladder cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Context:
- Bladder cancer exhibits resistance to doxorubicin chemotherapy.
- Chemotherapy resistance is often associated with cellular changes like the epithelial-mesenchymal transition (EMT).
- Fibroblast growth factor receptor 2 (FGFR2) is implicated in various cellular processes, including cancer progression.
Purpose:
- To investigate the role of the FGFR2 splice variant FGFR2IIIc in regulating mesenchymal-epithelial transition (MET) in doxorubicin-resistant bladder cancer cells.
- To determine the expression levels of FGFR2IIIc and associated proteins in chemoresistant cells.
- To assess the impact of FGFR2IIIc on cellular migration.
Summary:
- Doxorubicin-resistant bladder cancer cells (253J/DOX) were generated and characterized.
- Increased expression of P-glycoprotein and FGFR2IIIc was observed in resistant cells.
- Resistant cells showed upregulation of E-cadherin, downregulation of vimentin, and reduced migration, indicating MET.
Impact:
- FGFR2IIIc-induced MET in chemoresistant bladder cancer cells may be a key factor in the formation of metastatic lesions.
- Understanding this mechanism could lead to novel therapeutic strategies for overcoming chemoresistance and preventing metastasis in bladder cancer.
- This research highlights the potential of targeting FGFR2IIIc to manage advanced or metastatic bladder cancer.
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