Unknown

Dataset Information

0

Large-scale analysis of protein expression changes in human keratinocytes immortalized by human papilloma virus type 16 E6 and E7 oncogenes.


ABSTRACT: BACKGROUND:Infection with high-risk type human papilloma viruses (HPVs) is associated with cervical carcinomas and with a subset of head and neck squamous cell carcinomas. Viral E6 and E7 oncogenes cooperate to achieve cell immortalization by a mechanism that is not yet fully understood. Here, human keratinocytes were immortalized by long-term expression of HPV type 16 E6 or E7 oncoproteins, or both. Proteomic profiling was used to compare expression levels for 741 discrete protein features. RESULTS:Six replicate measurements were performed for each group using two-dimensional difference gel electrophoresis (2D-DIGE). The median within-group coefficient of variation was 19-21%. Significance of between-group differences was tested based on Significance Analysis of Microarray and fold change. Expression of 170 (23%) of the protein features changed significantly in immortalized cells compared to primary keratinocytes. Most of these changes were qualitatively similar in cells immortalized by E6, E7, or E6/7 expression, indicating convergence on a common phenotype, but fifteen proteins (~2%) were outliers in this regulatory pattern. Ten demonstrated opposite regulation in E6- and E7-expressing cells, including the cell cycle regulator p16INK4a; the carbohydrate binding protein Galectin-7; two differentially migrating forms of the intermediate filament protein Cytokeratin-7; HSPA1A (Hsp70-1); and five unidentified proteins. Five others had a pattern of expression that suggested cooperativity between the co-expressed oncoproteins. Two of these were identified as forms of the small heat shock protein HSPB1 (Hsp27). CONCLUSION:This large-scale analysis provides a framework for understanding the cooperation between E6 and E7 oncoproteins in HPV-driven carcinogenesis.

SUBMITTER: Merkley MA 

PROVIDER: S-EPMC2744660 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Large-scale analysis of protein expression changes in human keratinocytes immortalized by human papilloma virus type 16 E6 and E7 oncogenes.

Merkley Mark A MA   Hildebrandt Ellen E   Podolsky Robert H RH   Arnouk Hilal H   Ferris Daron G DG   Dynan William S WS   Stöppler Hubert H  

Proteome science 20090823


<h4>Background</h4>Infection with high-risk type human papilloma viruses (HPVs) is associated with cervical carcinomas and with a subset of head and neck squamous cell carcinomas. Viral E6 and E7 oncogenes cooperate to achieve cell immortalization by a mechanism that is not yet fully understood. Here, human keratinocytes were immortalized by long-term expression of HPV type 16 E6 or E7 oncoproteins, or both. Proteomic profiling was used to compare expression levels for 741 discrete protein featu  ...[more]

Similar Datasets

| S-EPMC4437748 | biostudies-literature
| S-EPMC18715 | biostudies-literature
2019-03-18 | PXD012186 | Pride
| S-EPMC8402821 | biostudies-literature
| S-EPMC8185923 | biostudies-literature
| S-EPMC8228617 | biostudies-literature
| S-EPMC4337564 | biostudies-literature
2013-11-27 | GSE14051 | GEO
| S-EPMC6032416 | biostudies-literature
| S-EPMC6728585 | biostudies-literature