Gene expression signatures modulated by epidermal growth factor receptor activation and their relationship to cetuximab resistance in head and neck squamous cell carcinoma
書誌事項
- 公開日
- 2012
- 資源種別
- journal article
- DOI
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- 10.1186/1471-2164-13-160
- 公開者
- Springer Science and Business Media LLC
この論文をさがす
説明
Aberrant activation of signaling pathways downstream of epidermal growth factor receptor (EGFR) has been hypothesized to be one of the mechanisms of cetuximab (a monoclonal antibody against EGFR) resistance in head and neck squamous cell carcinoma (HNSCC). To infer relevant and specific pathway activation downstream of EGFR from gene expression in HNSCC, we generated gene expression signatures using immortalized keratinocytes (HaCaT) subjected to ligand stimulation and transfected with EGFR, RELA/p65, or HRASVal12D.The gene expression patterns that distinguished the HaCaT variants and conditions were inferred using the Markov chain Monte Carlo (MCMC) matrix factorization algorithm Coordinated Gene Activity in Pattern Sets (CoGAPS). This approach inferred gene expression signatures with greater relevance to cell signaling pathway activation than the expression signatures inferred with standard linear models. Furthermore, the pathway signature generated using HaCaT-HRASVal12D further associated with the cetuximab treatment response in isogenic cetuximab-sensitive (UMSCC1) and -resistant (1CC8) cell lines.Our data suggest that the CoGAPS algorithm can generate gene expression signatures that are pertinent to downstream effects of receptor signaling pathway activation and potentially be useful in modeling resistance mechanisms to targeted therapies.
収録刊行物
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- BMC Genomics
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BMC Genomics 13 (1), 160-, 2012
Springer Science and Business Media LLC
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キーワード
- Keratinocytes
- Drug Resistance
- Cetuximab
- QH426-470
- Antibodies, Monoclonal, Humanized
- Antibodies
- Cell Line
- Cell Line, Tumor
- Monoclonal
- 616
- Genetics
- Humans
- Tumor
- Epidermal Growth Factor
- Carcinoma
- Antibodies, Monoclonal
- ErbB Receptors
- Squamous Cell
- Oncology
- Drug Resistance, Neoplasm
- Head and Neck Neoplasms
- Carcinoma, Squamous Cell
- Neoplasm
- TP248.13-248.65
- Algorithms
- Receptor
- Biotechnology
- Research Article
- Protein Binding
- Signal Transduction
詳細情報 詳細情報について
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- CRID
- 1360002218968015488
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- ISSN
- 14712164
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- PubMed
- 22549044
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- 資料種別
- journal article
-
- データソース種別
-
- Crossref
- KAKEN
- OpenAIRE
