Abstract P207: Role of (Pro)Renin Receptor in the Pathogenesis of Colon Cancer
(Pro)renin receptor ((P)RR) is a component of the Wnt receptor complex (Science, 2010). We have recently demonstrated that (P)RR plays an important role in the tumorigenesis of pancreatic ductal adenocarcinoma via the activation of Wnt/β-catenin signaling pathway (Shibayama et al. Sci Rep. 2015). Since the patients with colon cancer often show aberrantly activated Wnt/β-catenin-dependent signaling pathway by the mutations of its components, we investigated the possible role of (P)RR and Wnt/β-catenin signaling pathway in carcinogenesis of colon cancer. Real-time PCR was used for measuring mRNA levels of (P)RR. Protein levels of (P)RR was determined by Western blotting and immunohistochemistry. Activated β-catenin levels were determined by Western blotting. Cell proliferative ability was evaluated by counting the cell number in cultured colon cancer cell lines, HCT116 and DLD-1 cells. As compared to normal colon tissues (n=6), mRNA and protein levels of (P)RR were increased by 2.6- and 2.2-fold, respectively, in colon cancer tissues (n=9), which were associated with increased activated β-catenin levels (by 2.8-fold, P<0.05). However, plasma soluble (P)RR levels were not changed in patients with colon cancer (n=9). (P)RR and activated β-catenin levels were also increased in HCT116 (by 2.2- and 2.7-fold, n=5, respectively) and DLD-1 cells (by 1.9- and 2.8-fold, n=5, respectively). In these cells, inhibiting (P)RR with an siRNA attenuated the activity of β-catenin and reduced the proliferative abilities (n=5, P<0.05, respectively). These data suggest that (P)RR contributes to the tumorigenesis of colon cancer through the activation of Wnt/β-catenin signaling pathway.
Author Disclosures: A. Nishiyama: B. Research Grant (includes principal investigator, collaborator, or consultant and pending grants as well as grants already received); Modest; Collaborative studies or research grants; Daiichi-Sankyo Co. Ltd., Novartis Co. Ltd., Taisho-Toyama Pharm. Co. Ltd., Chu-gai Pharm. Co., Ltd., Ajinomoto Pharm. Co., Ltd., Mochida Pharma. Co., Ltd.. C. Other Research Support (includes receipt of drugs, supplies, equipment or other in-kind support); Modest; Drug compounds were provided by Ajinomoto Pharm. Co. Ltd., Daiichi-Sankyo Co. Ltd., Novartis A.G., Taisho-Toyama Pharm. Co. Ltd., Boehringer-Ingelheim Co., Ltd.. D. Speaker (includes speakers bureau, symposia, and expert witness); Modest; Mochida Pharm. Co. Ltd., Daiichi-Sankyo Co. Ltd., Taisho-Toyama Pharm. Co. Ltd., Boehringer-Ingelheim Co., Ltd., Pfizer Co., Ltd., Novartis Co. Ltd.. J. Wang: None. S. Yachida: None. G. Nguyen: None. T. Hirose: None. Y. Shibayama: None.
- © 2015 by American Heart Association, Inc.