Heterogeneous activation of the TGFβ pathway in glioblastomas identified by gene expression-based classification using TGFβ-responsive genes
<p>Abstract</p> <p>Background</p> <p>TGFβ has emerged as an attractive target for the therapeutic intervention of glioblastomas. Aberrant TGFβ overproduction in glioblastoma and other high-grade gliomas has been reported, however, to date, none of these reports has syst...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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BMC
2009-02-01
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| Series: | Journal of Translational Medicine |
| Online Access: | http://www.translational-medicine.com/content/7/1/12 |
| _version_ | 1818564302305492992 |
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| author | Xu Xie L Kapoun Ann M |
| author_facet | Xu Xie L Kapoun Ann M |
| author_sort | Xu Xie L |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>TGFβ has emerged as an attractive target for the therapeutic intervention of glioblastomas. Aberrant TGFβ overproduction in glioblastoma and other high-grade gliomas has been reported, however, to date, none of these reports has systematically examined the components of TGFβ signaling to gain a comprehensive view of TGFβ activation in large cohorts of human glioma patients.</p> <p>Methods</p> <p>TGFβ activation in mammalian cells leads to a transcriptional program that typically affects 5–10% of the genes in the genome. To systematically examine the status of TGFβ activation in high-grade glial tumors, we compiled a gene set of transcriptional response to TGFβ stimulation from tissue culture and <it>in vivo </it>animal studies. These genes were used to examine the status of TGFβ activation in high-grade gliomas including a large cohort of glioblastomas. Unsupervised and supervised classification analysis was performed in two independent, publicly available glioma microarray datasets.</p> <p>Results</p> <p>Unsupervised and supervised classification using the TGFβ-responsive gene list in two independent glial tumor gene expression data sets revealed various levels of TGFβ activation in these tumors. Among glioblastomas, one of the most devastating human cancers, two subgroups were identified that showed distinct TGFβ activation patterns as measured from transcriptional responses. Approximately 62% of glioblastoma samples analyzed showed strong TGFβ activation, while the rest showed a weak TGFβ transcriptional response.</p> <p>Conclusion</p> <p>Our findings suggest heterogeneous TGFβ activation in glioblastomas, which may cause potential differences in responses to anti-TGFβ therapies in these two distinct subgroups of glioblastomas patients.</p> |
| first_indexed | 2024-12-14T01:27:17Z |
| format | Article |
| id | doaj.art-ccf6bc2123544d87bb2dbbf1f5e15392 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-14T01:27:17Z |
| publishDate | 2009-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-ccf6bc2123544d87bb2dbbf1f5e153922022-12-21T23:22:09ZengBMCJournal of Translational Medicine1479-58762009-02-01711210.1186/1479-5876-7-12Heterogeneous activation of the TGFβ pathway in glioblastomas identified by gene expression-based classification using TGFβ-responsive genesXu Xie LKapoun Ann M<p>Abstract</p> <p>Background</p> <p>TGFβ has emerged as an attractive target for the therapeutic intervention of glioblastomas. Aberrant TGFβ overproduction in glioblastoma and other high-grade gliomas has been reported, however, to date, none of these reports has systematically examined the components of TGFβ signaling to gain a comprehensive view of TGFβ activation in large cohorts of human glioma patients.</p> <p>Methods</p> <p>TGFβ activation in mammalian cells leads to a transcriptional program that typically affects 5–10% of the genes in the genome. To systematically examine the status of TGFβ activation in high-grade glial tumors, we compiled a gene set of transcriptional response to TGFβ stimulation from tissue culture and <it>in vivo </it>animal studies. These genes were used to examine the status of TGFβ activation in high-grade gliomas including a large cohort of glioblastomas. Unsupervised and supervised classification analysis was performed in two independent, publicly available glioma microarray datasets.</p> <p>Results</p> <p>Unsupervised and supervised classification using the TGFβ-responsive gene list in two independent glial tumor gene expression data sets revealed various levels of TGFβ activation in these tumors. Among glioblastomas, one of the most devastating human cancers, two subgroups were identified that showed distinct TGFβ activation patterns as measured from transcriptional responses. Approximately 62% of glioblastoma samples analyzed showed strong TGFβ activation, while the rest showed a weak TGFβ transcriptional response.</p> <p>Conclusion</p> <p>Our findings suggest heterogeneous TGFβ activation in glioblastomas, which may cause potential differences in responses to anti-TGFβ therapies in these two distinct subgroups of glioblastomas patients.</p>http://www.translational-medicine.com/content/7/1/12 |
| spellingShingle | Xu Xie L Kapoun Ann M Heterogeneous activation of the TGFβ pathway in glioblastomas identified by gene expression-based classification using TGFβ-responsive genes Journal of Translational Medicine |
| title | Heterogeneous activation of the TGFβ pathway in glioblastomas identified by gene expression-based classification using TGFβ-responsive genes |
| title_full | Heterogeneous activation of the TGFβ pathway in glioblastomas identified by gene expression-based classification using TGFβ-responsive genes |
| title_fullStr | Heterogeneous activation of the TGFβ pathway in glioblastomas identified by gene expression-based classification using TGFβ-responsive genes |
| title_full_unstemmed | Heterogeneous activation of the TGFβ pathway in glioblastomas identified by gene expression-based classification using TGFβ-responsive genes |
| title_short | Heterogeneous activation of the TGFβ pathway in glioblastomas identified by gene expression-based classification using TGFβ-responsive genes |
| title_sort | heterogeneous activation of the tgfβ pathway in glioblastomas identified by gene expression based classification using tgfβ responsive genes |
| url | http://www.translational-medicine.com/content/7/1/12 |
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