Developmentally Imprinted Genes as Markers for Bladder Tumor Progression |
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Authors: | Mark J Cooper Martin Fischer Dymitr Komitowski Alexander Shevelev Ekkehard Schulze Ilana Ariel Mark L Tykocinski Stela Miron Joseph Ilan Nathan De Groot Abraham Hochberg |
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Institution: | aFrom the Departments of Medicine and Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio; the German Cancer Research Center, Heidelberg, Germany; the Department of Pathology, Hadassah University Hospital, Mount Scopus, and the Department of Biological Chemistry, The Silberman Institute of Life Sciences, Hebrew University, Jerusalem, Israel. |
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Abstract: | PurposeDevelopmentally imprinted genes, such as H19 and insulin-like growth factor-II (IGF-II), play an important role during human embryogenesis and also have been implicated in the pathogenesis of embryonal tumors of childhood. Since H19 is expressed in human fetal bladder, we evaluated 35 bladder carcinomas for H19 expression by in situ hybridization analysis and correlated expression with tumor grade. As a prelude to gene transfer studies to determine if H19 is a bladder tumor oncogene, we also evaluated bladder cell lines for expression of H19, IGF-II, IGF-I and the type I IGF receptor.Materials and MethodsH19 expression was evaluated by in situ hybridization analysis in bladder tumor specimens. Northern analysis was used to evaluate the expression of H19, IGF-II, IGF-I and the type I IGF receptor in bladder cell lines.ResultsH19 was expressed preferentially in advanced stage tumors: 2 of 12 grade I tumors were H19 positive, whereas 9 of 11 grade II and 7 of 10 grade III tumors expressed H19 (p = 0.004). Additionally, 6 of 6 carcinoma in situ tumors were H19 positive, whereas normal bladder mucosa cells were H19 negative. We found that 3 of 11 cell lines (HT-1376, HT-1197 and 5637) express high levels of H19 mRNA, and each of these cell lines and J82 also express IGF-II. All cell lines examined expressed the type I IGF receptor, whereas there was no detectable IGF-I mRNA.ConclusionsThese data demonstrate that H19 is an oncodevelopmental marker of bladder tumor progression and raise the possibility that H19 may have oncogenic properties in bladder cancer. |
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