Glioblastoma-specific protein interaction network identifies PP1A and CSK21 as connecting molecules between cell cycle-associated genes.
| Autor: | Ladha J; Chromatin Biology Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Institute of Bioinformatics and Applied Biotechnology, Bangalore, India., Donakonda S, Agrawal S, Thota B, Srividya MR, Sridevi S, Arivazhagan A, Thennarasu K, Balasubramaniam A, Chandramouli BA, Hegde AS, Kondaiah P, Somasundaram K, Santosh V, Rao SM |
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| Jazyk: | angličtina |
| Zdroj: | Cancer research [Cancer Res] 2010 Aug 15; Vol. 70 (16), pp. 6437-47. Date of Electronic Publication: 2010 Jul 27. |
| DOI: | 10.1158/0008-5472.CAN-10-0819 |
| Abstrakt: | 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 alpha (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. ((c)2010 AACR.) |
| Databáze: | MEDLINE |
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