Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins

BMC Cancer

Research Article

Manfred Schartl¹  Svenja Meierjohann¹  Johannes M Haydn¹  Janka Teutschbein²  Martin Eilers³  Michael Krause⁴  Birgit Samans⁵ 

[1] Department of Physiological Chemistry I, Biocenter, University of Wurzburg, Wurzburg, Germany;Department of Physiological Chemistry I, Biocenter, University of Wurzburg, Wurzburg, Germany;Department of Molecular and Applied Microbiology, Leibniz-Institute for Natural Product Research and Infection Biology - Hans-Knoell-Institute, Jena, Germany;Department of Physiological Chemistry II, Biocenter, University of Wurzburg, Wurzburg, Germany;Institute of Molecular Biology and Tumor Research (IMT), University of Marburg, Marburg, Germany;Institute of Molecular Biology and Tumor Research (IMT), University of Marburg, Marburg, Germany;Biometry and Population Genetics, Justus Liebig University Giessen, Germany;

关键词: Melanoma;    Melanoma Cell Line;    Human Melanoma Cell Line;    Bosutinib;    Expression Analysis Systematic Explorer;   

DOI  :  10.1186/1471-2407-10-386

 received in 2010-04-13, accepted in 2010-07-21,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundMelanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the Xiphophorus melanoma model system, a mutated version of the EGF receptor Xmrk (Xiphophorus melanoma receptor kinase) triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation.MethodsHere, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene FOSL1 was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated.ResultsGenes with the strongest upregulation after receptor activation were FOS-like antigen 1 (Fosl1), early growth response 1 (Egr1), osteopontin (Opn), insulin-like growth factor binding protein 3 (Igfbp3), dual-specificity phosphatase 4 (Dusp4), and tumor-associated antigen L6 (Taal6). Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that FOSL1, OPN, IGFBP3, DUSP4, and TAAL6 also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of FOSL1 in human melanoma cell lines reduced their proliferation and migration.ConclusionAltogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute new possible molecular players in melanoma development. Specifically, a role of FOSL1 in melanomagenic processes is demonstrated. These data are the basis for future detailed analyses of the investigated target genes.

【 授权许可】

Unknown   
© Teutschbein et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.