Gene Expression Profiling of ERBB Receptors and Ligands in Human Transitional Cell Carcinoma of the Bladder

No AccessJournal of UrologyInvestigative urology1 Mar 2006Gene Expression Profiling of ERBB Receptors and Ligands in Human Transitional Cell Carcinoma of the Bladderis companion ofNovel Approach of Human Epidermal Growth Factor Receptor 2 Detection in Noninvasive and Invasive Transitional Cell Carcinoma of the Bladder Delphine Amsellem-Ouazana, Ivan Bièche, Sengül Tozlu, Henry Botto, Bernard Debré, and Rosette Lidereau Delphine Amsellem-OuazanaDelphine Amsellem-Ouazana Department of Urology, Hôpital Cochin, Paris, France , Ivan BiècheIvan Bièche Genetic Oncology-INSERM U735, Centre René Huguenin, Saint-Cloud, France , Sengül TozluSengül Tozlu Genetic Oncology-INSERM U735, Centre René Huguenin, Saint-Cloud, France , Henry BottoHenry Botto Department of Urology, Hôpital Foch, Suresnes, France , Bernard DebréBernard Debré Department of Urology, Hôpital Cochin, Paris, France , and Rosette LidereauRosette Lidereau Genetic Oncology-INSERM U735, Centre René Huguenin, Saint-Cloud, France View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)00317-4AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The ErbB driven growth pathway has been implicated in most human epithelial malignancies. Therefore, its blockade is a promising therapeutic strategy and several candidate drugs are currently undergoing clinical trials. Paradoxically little is known of the expression pattern or clinical significance of the 4 ErbB receptors and their 11 ligands in TCC of the bladder. Materials and Methods: To obtain further insight into the molecular pathogenesis of TCC we used quantitative real-time reverse transcriptase-polymerase chain reaction assay to quantify mRNA expression of the 4 ERBB and their 11 known ligand genes, including recently described EPGN/epigen, in 73 tumor samples. Results: The level of mRNA of 4 ligand genes (EGF, NRG1, NRG2 and NRG3) was extremely low, that is detectable but not quantifiable. Six genes were over expressed (ERBB2, TGFA, HB-EGF, AREG, EREG and EPGN), 3 were under expressed (ERBB1, ERBB4 and NRG4) and 2 were over or under expressed (ERBB3 and BTC). ERBB2 and AREG expression differed between early stage tumors (pTa grade 1) and normal samples. The most marked differences in expression were ERBB3, EREG and NRG4 between superficial and muscle invasive tumors (p = 0.0069, 0.00007 and 0.0000001, respectively), and TGFA and NRG4 between low and high grade superficial tumors, and between pT1 or greater and pTa tumors. Conclusions: This study shows the involvement of the ERBB family and ligand genes in TCC. Most receptor and ligand genes are deregulated at different stages of carcinogenesis, implying that they should be studied simultaneously. Quantitative real-time reverse transcriptase-polymerase chain reaction could be used to determine ErbB signaling pathway status in individuals with a view to tailored therapy. References 1 : Untangling the ErbB signalling network. Nat Rev Mol Cell Biol2001; 2: 127. Google Scholar 2 : Cloning and biological activity of epigen, a novel member of the epidermal growth factor superfamily. J Biol Chem2001; 276: 18265. Google Scholar 3 : The ErbB receptor family: a therapeutic target for cancer. Trends Mol Med2002; 8: S19. Google Scholar 4 : Molecular biology of transitional cell carcinoma. Crit Rev Oncol Hematol2003; 47: 181. Google Scholar 5 : Molecular prognostication in bladder cancer—a current perspective. Eur J Cancer2003; 39: 1501. Google Scholar 6 : Novel approaches with targeted therapies in bladder cancer. Therapy of bladder cancer by blockade of the epidermal growth factor receptor family. Crit Rev Oncol Hematol2003; 46: 85. Google Scholar 7 : Management of primary resistance to gemcitabine and cisplatin (G-C) chemotherapy in metastatic bladder cancer with HER2 over-expression. Ann Oncol2004; 15: 538. Google Scholar 8 : Prognostic value of ERBB family mRNA expression in breast carcinomas. Int J Cancer2003; 106: 758. Google Scholar 9 : DNA, RNA and immunohistochemical characterization of the HER-2/neu oncogene in transitional cell carcinoma of the bladder. J Urol1991; 146: 1398. Abstract, Google Scholar 10 : A subclass of HER1 ligands are prognostic markers for survival in bladder cancer patients. Cancer Res2001; 61: 6227. Google Scholar 11 : HER2 overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic implications. Int J Cancer2002; 102: 514. Google Scholar 12 : Expression profiles of ErbB family receptors and prognosis in primary transitional cell carcinoma of the urinary bladder. Clin Cancer Res2001; 7: 1957. Google Scholar 13 : c-erbB-2 in bladder cancer: molecular biology, correlation with epidermal growth factor receptors and prognostic value. J Urol1996; 155: 321. Link, Google Scholar 14 : A nuclear form of the heparin-binding epidermal growth factor-like growth factor precursor is a feature of aggressive transitional cell carcinoma. Cancer Res2003; 63: 484. Google Scholar 15 : Fluorescence in situ hybridization evaluation of c-erbB-2 gene amplification and chromosomal anomalies in bladder cancer. Clin Cancer Res2001; 7: 2463. Google Scholar 16 : HER-2/neu protein overexpression and gene amplification in human transitional cell carcinoma of the bladder. Urology2004; 63: 786. Google Scholar 17 : Real-time reverse transcription-PCR assay for future management of ERBB2-based clinical applications. Clin Chem1999; 45: 1148. Google Scholar 18 : Identification of patients with transitional cell carcinoma of the bladder overexpressing ErbB2, ErbB3, or specific ErbB4 isoforms: real-time reverse transcription-PCR analysis in estimation of ErbB receptor status from cancer patients. Clin Cancer Res2003; 9: 5346. Google Scholar 19 : Expression of HER3, HER4 and their ligand heregulin-4 is associated with better survival in bladder cancer patients. Br J Cancer2004; 91: 2034. Google Scholar 20 : Expression of transforming growth factor alpha and epidermal growth factor receptor in human bladder cancer. Scand J Clin Lab Invest1999; 59: 267. Google Scholar © 2006 by American Urological AssociationFiguresReferencesRelatedDetailsCited byMooso B, Vinall R, Mudryj M, Yap S, deVere White R and Ghosh P (2014) The Role of EGFR Family Inhibitors in Muscle Invasive Bladder Cancer: A Review of Clinical Data and Molecular EvidenceJournal of Urology, VOL. 193, NO. 1, (19-29), Online publication date: 1-Jan-2015.Kassouf W, Black P, Tuziak T, Bondaruk J, Lee S, Brown G, Adam L, Wei C, Baggerly K, Bar-Eli M, McConkey D, Czerniak B and Dinney C (2007) Distinctive Expression Pattern of ErbB Family Receptors Signifies an Aggressive Variant of Bladder CancerJournal of Urology, VOL. 179, NO. 1, (353-358), Online publication date: 1-Jan-2008.Related articlesJournal of Urology9 Nov 2018Novel Approach of Human Epidermal Growth Factor Receptor 2 Detection in Noninvasive and Invasive Transitional Cell Carcinoma of the Bladder Volume 175Issue 3March 2006Page: 1127-1132 Advertisement Copyright & Permissions© 2006 by American Urological AssociationKeywordsgene expression profilingbladderbladder neoplasmsMetricsAuthor Information Delphine Amsellem-Ouazana Department of Urology, Hôpital Cochin, Paris, France More articles by this author Ivan Bièche Genetic Oncology-INSERM U735, Centre René Huguenin, Saint-Cloud, France More articles by this author Sengül Tozlu Genetic Oncology-INSERM U735, Centre René Huguenin, Saint-Cloud, France More articles by this author Henry Botto Department of Urology, Hôpital Foch, Suresnes, France More articles by this author Bernard Debré Department of Urology, Hôpital Cochin, Paris, France More articles by this author Rosette Lidereau Genetic Oncology-INSERM U735, Centre René Huguenin, Saint-Cloud, France More articles by this author Expand All Advertisement PDF downloadLoading ...