BACKGROUND: The identification of potential tumor markers will help improve therapeutic planning and patient management. Therefore, the aim of this study was to highlight the role of DNA methyltransferase 1 (DNMT1) in bladder cancer. METHODS: A total of 50 samples of nonmalignant urothelium, 65 of muscle-invasive bladder cancers, 15 of distant metastasis, and 50 of nonmuscle-invasive bladder cancers were selected for immunohistochemical staining analysis. Furthermore, human bladder cancer cell lines HT1376 and HT1197 were selected for cell and animal experiments investigating changes in tumor behavior, treatment response, and related signaling in bladder cancer. RESULTS: The incidence of nuclear DNMT1 immunoreactivity in the bladder cancer specimens (45%) was significantly higher than in nonmalignant urothelium (15%, P = .0005), and the incidence in cancer was positively linked to clinical stage (24% in ≤T1 vs 55% in T2-T4, P = .0007). The staining of DNMT1 was also significantly linked to lower complete response rates (P = .0014) and reduced survival rates (P = .000). By in vitro and in vivo experiments, DNMT1 silencing vector reduced tumor growth and attenuated treatment resistance in bladder cancer cells. Less epithelial-mesenchymal transition, less invasion, and slower tumor growth were noted in cancer cells with inhibited DNMT1. Furthermore, the epidermal growth factor receptor-mediated phosphatidylinositol 3'-kinase-protein kinase B pathway might be the mechanism underlying the effects of DNMT1 on bladder cancer. CONCLUSIONS: DNMT1 could be a significant clinical predictor for stage and treatment response of bladder cancer. Moreover, targeting this enzyme could be a promising strategy for treating bladder cancer, as evidenced by inhibited tumor growth and enhanced radiosensitivity.
BACKGROUND: The identification of potential tumor markers will help improve therapeutic planning and patient management. Therefore, the aim of this study was to highlight the role of DNA methyltransferase 1 (DNMT1) in bladder cancer. METHODS: A total of 50 samples of nonmalignant urothelium, 65 of muscle-invasive bladder cancers, 15 of distant metastasis, and 50 of nonmuscle-invasive bladder cancers were selected for immunohistochemical staining analysis. Furthermore, humanbladder cancer cell lines HT1376 and HT1197 were selected for cell and animal experiments investigating changes in tumor behavior, treatment response, and related signaling in bladder cancer. RESULTS: The incidence of nuclear DNMT1 immunoreactivity in the bladder cancer specimens (45%) was significantly higher than in nonmalignant urothelium (15%, P = .0005), and the incidence in cancer was positively linked to clinical stage (24% in ≤T1 vs 55% in T2-T4, P = .0007). The staining of DNMT1 was also significantly linked to lower complete response rates (P = .0014) and reduced survival rates (P = .000). By in vitro and in vivo experiments, DNMT1 silencing vector reduced tumor growth and attenuated treatment resistance in bladder cancer cells. Less epithelial-mesenchymal transition, less invasion, and slower tumor growth were noted in cancer cells with inhibited DNMT1. Furthermore, the epidermal growth factor receptor-mediated phosphatidylinositol 3'-kinase-protein kinase B pathway might be the mechanism underlying the effects of DNMT1 on bladder cancer. CONCLUSIONS:DNMT1 could be a significant clinical predictor for stage and treatment response of bladder cancer. Moreover, targeting this enzyme could be a promising strategy for treating bladder cancer, as evidenced by inhibited tumor growth and enhanced radiosensitivity.
Authors: Sabine A S Langie; Gudrun Koppen; Daniel Desaulniers; Fahd Al-Mulla; Rabeah Al-Temaimi; Amedeo Amedei; Amaya Azqueta; William H Bisson; Dustin G Brown; Gunnar Brunborg; Amelia K Charles; Tao Chen; Annamaria Colacci; Firouz Darroudi; Stefano Forte; Laetitia Gonzalez; Roslida A Hamid; Lisbeth E Knudsen; Luc Leyns; Adela Lopez de Cerain Salsamendi; Lorenzo Memeo; Chiara Mondello; Carmel Mothersill; Ann-Karin Olsen; Sofia Pavanello; Jayadev Raju; Emilio Rojas; Rabindra Roy; Elizabeth P Ryan; Patricia Ostrosky-Wegman; Hosni K Salem; A Ivana Scovassi; Neetu Singh; Monica Vaccari; Frederik J Van Schooten; Mahara Valverde; Jordan Woodrick; Luoping Zhang; Nik van Larebeke; Micheline Kirsch-Volders; Andrew R Collins Journal: Carcinogenesis Date: 2015-06 Impact factor: 4.944
Authors: Alan P Lombard; Benjamin A Mooso; Stephen J Libertini; Rebecca M Lim; Rachel M Nakagawa; Kathleen D Vidallo; Nicole C Costanzo; Paramita M Ghosh; Maria Mudryj Journal: Mol Carcinog Date: 2015-04-11 Impact factor: 4.784
Authors: Feng Jin; Jose Thaiparambil; Sri Ramya Donepudi; Venkatrao Vantaku; Danthasinghe Waduge Badrajee Piyarathna; Suman Maity; Rashmi Krishnapuram; Vasanta Putluri; Franklin Gu; Preeti Purwaha; Salil Kumar Bhowmik; Chandrashekar R Ambati; Friedrich-Carl von Rundstedt; Florian Roghmann; Sebastian Berg; Joachim Noldus; Kimal Rajapakshe; Daniel Gödde; Stephan Roth; Stephan Störkel; Stephan Degener; George Michailidis; Benny Abraham Kaipparettu; Balasubramanyam Karanam; Martha K Terris; Shyam M Kavuri; Seth P Lerner; Farrah Kheradmand; Cristian Coarfa; Arun Sreekumar; Yair Lotan; Randa El-Zein; Nagireddy Putluri Journal: Cancer Prev Res (Phila) Date: 2017-08-29
Authors: Wan Faiziah Wan Abdul Rahman; Khairul Shakir Ab Rahman; Siti Norasikin Mohd Nafi; Mohd Hashairi Fauzi; Hasnan Jaafar Journal: Int J Clin Exp Pathol Date: 2015-06-01