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Proteome profiling of keratinocytes transforming to malignancy.
- Source :
-
Electrophoresis [Electrophoresis] 2015 Feb; Vol. 36 (4), pp. 564-76. Date of Electronic Publication: 2015 Jan 28. - Publication Year :
- 2015
-
Abstract
- To shed light on the multistep process of squamous cell carcinoma development and the underlying pathologic mechanisms, we performed comparative proteome analysis of keratinocytes, keratinocytes stimulated with Il-1beta, and A431 epidermoid carcinoma cells. Fractionation of the cells into supernatant, nucleus, and cytoplasm was followed by protein separation, proteolytic digest, and nano-LC separation, and fragmentation using an ion trap mass spectrometer. Specific bioinformatics tools were used to generate a list of keratinocyte-specific proteins. Ninety percent of these proteins were found to be upregulated in keratinocytes versus the A431 cells. Classification of the identified proteins by biologic function and gene set enrichment analysis revealed that keratinocytes produced more proteins involved in cell differentiation, cell adhesion, cell junction, calcium ion, calmodulin binding, cytoskeleton organization, and cytokinesis, whereas A431 produced more proteins involved in cell cycle checkpoint, cell cycle process, RNA processing and transport, DNA damage and repair, RNA and DNA binding, and chromatin remodeling. The protein signatures of A431 and normal keratinocytes treated with IL-1beta showed marked similarity, confirming that inflammation is an important step in malignant transformation in nonmelanoma skin cancer. Thus, proteome profiling and bioinformatic processing may support the understanding of the underlying mechanisms, with the potential to facilitate development of early biomarkers and patient-tailored therapy.<br /> (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- Carcinoma, Squamous Cell metabolism
Carcinoma, Squamous Cell pathology
Cell Transformation, Neoplastic
Cells, Cultured
Dermatitis metabolism
High-Throughput Screening Assays methods
Humans
Interleukin-1beta pharmacology
Keratinocytes drug effects
Proteome metabolism
Reference Values
Skin Neoplasms metabolism
Skin Neoplasms pathology
Tumor Cells, Cultured
Keratinocytes metabolism
Keratinocytes pathology
Proteome analysis
Proteomics methods
Subjects
Details
- Language :
- English
- ISSN :
- 1522-2683
- Volume :
- 36
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Electrophoresis
- Publication Type :
- Academic Journal
- Accession number :
- 25395074
- Full Text :
- https://doi.org/10.1002/elps.201400309