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Restoration of Bone Morphogenetic Protein Receptor Type II Expression Leads to a Decreased Rate of Tumor Growth in Bladder Transitional Cell Carcinoma Cell Line TSU-Pr1

¹ Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland; ² Department of Urology, Ewha Women’s University, Seoul, Korea; ³ Department of Urology, Chungbuk National University Hospital, Cheongju, Korea; ⁴ Scott Department of Urology, Baylor College of Medicine, Houston, Texas; and ⁵ Department of Urology, University of California, Irvine, California

Bone morphogenetic proteins (BMPs), potential regulators of cellular growth and metastasis that signal through an interaction with plasma membrane receptors, have been suggested to be important regulators of malignant cells. The present study was carried out to evaluate the potential role of BMP receptor (BMP-R) types IA, IB, and II in bladder transitional cell carcinoma (TCC) cells. Initially, we investigated the expression of these BMP-Rs in 30 archival tissues of human bladder TCC using immunohistochemistry; 10 benign bladder specimens were used for comparison. The results demonstrated that the expression of BMP-Rs is localized preferentially to the transitional epithelium and that there was a significant association between loss of BMP-RII expression and tumor grade. To find a cell line that can serve as a model system for clinical observation, we subsequently examined sensitivity to BMP-4 and expression of BMP-RII, BMP-RIA, and BMP-RIB in three human bladder cancer cell lines, TCC-Sup, RT4, and TSU-Pr1. Of the three cell lines, TSU-Pr1 exhibited a decreased level of BMP-RII expression and was resistant to the growth-inhibitory effect of BMP-4. Overexpression of BMP-RII in TSU-Pr1 cells not only restored BMP-4 responsiveness but also significantly decreased tumorigenicity in vivo. Taken together, these results demonstrate that human bladder TCC tissues have a frequent loss of BMP-RII expression and that overexpression of BMP-RII leads to restoration of BMP signaling and decreased tumor growth in the human bladder TCC cell line TSU-Pr1.

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				W. Jin, C. Yun, H.-S. Kim, and S.-J. Kim TrkC Binds to the Bone Morphogenetic Protein Type II Receptor to Suppress Bone Morphogenetic Protein Signaling Cancer Res., October 15, 2007; 67(20): 9869 - 9877. [Abstract] [Full Text] [PDF]