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Higher Expression of Peroxisome Proliferator-activated Receptor γ or Its Activation by Agonist Thiazolidinedione-rosiglitazone Promotes Bladder Cancer Cell Migration and Invasion - 21/04/13

Doi : 10.1016/j.urology.2012.12.027 
Dong-Rong Yang a, b, Shin-Jen Lin a, Xian-Fan Ding a, c, Hiroshi Miyamoto a, Edward Messing a, Li-Qiong Li a, Nancy Wang a, Chawnshang Chang a, d,
a George H. Whipple Laboratory for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology, The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 
b Department of Urology, Second Affiliated Hospital of Soochow University, Suzhou, China 
c Department of Urology, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China 
d Sex Hormone Research Center, China Medical University and Hospital, Taichung, Taiwan 

Reprint requests: Chawnshang Chang, Ph.D., George H. Whipple Laboratory for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology, The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14646.

Abstract

Objective

To investigate the role of peroxisome proliferator-activated receptor γ (PPARγ) in bladder cancer (BCa) progression.

Materials and Methods

The gene copy number of PPARγ in human BCa tissue samples was analyzed by fluorescence in situ hybridization. The migration and invasive ability of human BCa cell lines with different PPARγ expression levels or treated with thiazolidinedione-rosiglitazone, a PPARγ agonist and an antidiabetic drug, were investigated.

Results

PPARγ amplification was increased dramatically in BCa tissue compared with normal urothelium (38.1% vs 4.3%, P = .0082) and in tumors with lymph node metastasis compared with those without metastasis (75.0% vs 15.4%, P = .0176). The human BCa cell line 5637 with strong PPARγ expression demonstrated a greater ability for cell migration and invasion than the UMUC-3 cell line with weak PPARγ expression. Knocking down PPARγ in BCa 5637 cells led to decreased cell migration, and activation of PPARγ with thiazolidinedione-rosiglitazone promoted their migration and invasive ability.

Conclusion

PPARγ amplification in BCa could play an important role in BCa cell migration and invasion. Alteration of PPARγ expression by PPARγ-small interfering ribonucleic acid or activation by its agonist rosiglitazone, a diabetic thiazolidinedione drug, could lead to alternation of BCa cell migration and invasion.

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Mappa


 Dong-Rong Yang, Shin-Jen Lin, Xian-Fan Ding are co-first authors.
 Financial Disclosure: The authors declare that they have no relevant financial interests.
 Funding Support: This work was supported by National Institutes of Health (grants CA155477 and CA156700), the George Whipple Professorship Endowment, and the Taiwan Department of Health Clinical Trial, Research Center of Excellence (grant DOH99-TD-B-111-004 to the China Medical University, Taichung, Taiwan).


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