Glioblastoma-specific protein interaction network identifies PP1A and CSK21 as connecting molecules between cell cycle-associated genes
| Autor: | Sainitin Donakonda, Balaram Thota, Satyanarayana M.R. Rao, Arimappamagan Arivazhagan, Kandavel Thennarasu, Mallavarapu R. Srividya, Vani Santosh, Kumaravel Somasundaram, Bangalore A. Chandramouli, Anandh Balasubramaniam, Shipra Agrawal, Paturu Kondaiah, S. Sridevi, Alangar Sattiyaranjandas Hegde, Jayashree S. Ladha |
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| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
Computational biology Biology Gene Expression Regulation Enzymologic Downregulation and upregulation Interaction network Protein Phosphatase 1 Protein Interaction Mapping medicine Humans Casein Kinase II Gene Microbiology & Cell Biology Molecular Reproduction Development & Genetics Brain Neoplasms Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Cancer Astrocytoma Protein phosphatase 1 Cell cycle medicine.disease Immunohistochemistry Up-Regulation Gene Expression Regulation Neoplastic Genes cdc Oncology Immunology Glioblastoma |
| Zdroj: | Cancer research. 70(16) |
| ISSN: | 1538-7445 |
| Popis: | Glioblastoma (GBM; grade IV astrocytoma) is a very aggressive form of brain cancer with a poor survival and few qualified predictive markers. This study integrates experimentally validated genes that showed specific upregulation in GBM along with their protein-protein interaction information. A system level analysis was used to construct GBM-specific network. Computation of topological parameters of networks showed scale-free pattern and hierarchical organization. From the large network involving 1,447 proteins, we synthesized subnetworks and annotated them with highly enriched biological processes. A careful dissection of the functional modules, important nodes, and their connections identified two novel intermediary molecules CSK21 and protein phosphatase 1 α (PP1A) connecting the two subnetworks CDC2-PTEN-TOP2A-CAV1-P53 and CDC2-CAV1-RB-P53-PTEN, respectively. Real-time quantitative reverse transcription-PCR analysis revealed CSK21 to be moderately upregulated and PP1A to be overexpressed by 20-fold in GBM tumor samples. Immunohistochemical staining revealed nuclear expression of PP1A only in GBM samples. Thus, CSK21 and PP1A, whose functions are intimately associated with cell cycle regulation, might play key role in gliomagenesis. Cancer Res; 70(16); 6437–47. ©2010 AACR. |
| Databáze: | OpenAIRE |
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