Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins
<p>Abstract</p> <p>Background</p> <p>Melanoma 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 <it>Xiphophorus...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2010-07-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/10/386 |
| _version_ | 1811252958910742528 |
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| author | Krause Michael Samans Birgit Haydn Johannes M Teutschbein Janka Eilers Martin Schartl Manfred Meierjohann Svenja |
| author_facet | Krause Michael Samans Birgit Haydn Johannes M Teutschbein Janka Eilers Martin Schartl Manfred Meierjohann Svenja |
| author_sort | Krause Michael |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Melanoma 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 <it>Xiphophorus </it>melanoma model system, a mutated version of the EGF receptor Xmrk (<it>Xiphophorus </it>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.</p> <p>Methods</p> <p>Here, 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 <it>FOSL1 </it>was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated.</p> <p>Results</p> <p>Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (<it>Fosl1</it>), early growth response 1 (<it>Egr1</it>), osteopontin (<it>Opn</it>), insulin-like growth factor binding protein 3 (<it>Igfbp3</it>), dual-specificity phosphatase 4 (<it>Dusp4</it>), and tumor-associated antigen L6 (<it>Taal6</it>). Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that <it>FOSL1</it>, <it>OPN</it>, <it>IGFBP3</it>, <it>DUSP4</it>, and <it>TAAL6 </it>also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of <it>FOSL1 </it>in human melanoma cell lines reduced their proliferation and migration.</p> <p>Conclusion</p> <p>Altogether, 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.</p> |
| first_indexed | 2024-04-12T16:43:37Z |
| format | Article |
| id | doaj.art-c245b4b07d9d4fe2bc434869a0f89289 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T16:43:37Z |
| publishDate | 2010-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-c245b4b07d9d4fe2bc434869a0f892892022-12-22T03:24:41ZengBMCBMC Cancer1471-24072010-07-0110138610.1186/1471-2407-10-386Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteinsKrause MichaelSamans BirgitHaydn Johannes MTeutschbein JankaEilers MartinSchartl ManfredMeierjohann Svenja<p>Abstract</p> <p>Background</p> <p>Melanoma 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 <it>Xiphophorus </it>melanoma model system, a mutated version of the EGF receptor Xmrk (<it>Xiphophorus </it>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.</p> <p>Methods</p> <p>Here, 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 <it>FOSL1 </it>was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated.</p> <p>Results</p> <p>Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (<it>Fosl1</it>), early growth response 1 (<it>Egr1</it>), osteopontin (<it>Opn</it>), insulin-like growth factor binding protein 3 (<it>Igfbp3</it>), dual-specificity phosphatase 4 (<it>Dusp4</it>), and tumor-associated antigen L6 (<it>Taal6</it>). Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that <it>FOSL1</it>, <it>OPN</it>, <it>IGFBP3</it>, <it>DUSP4</it>, and <it>TAAL6 </it>also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of <it>FOSL1 </it>in human melanoma cell lines reduced their proliferation and migration.</p> <p>Conclusion</p> <p>Altogether, 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.</p>http://www.biomedcentral.com/1471-2407/10/386 |
| spellingShingle | Krause Michael Samans Birgit Haydn Johannes M Teutschbein Janka Eilers Martin Schartl Manfred Meierjohann Svenja Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins BMC Cancer |
| title | Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins |
| title_full | Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins |
| title_fullStr | Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins |
| title_full_unstemmed | Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins |
| title_short | Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins |
| title_sort | gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins |
| url | http://www.biomedcentral.com/1471-2407/10/386 |
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