Gene expression analysis of PTEN positive glioblastoma stem cells identifies DUB3 and Wee1 modulation in a cell differentiation model

• Published in: PloS one Vol. 8; no. 12; p. e81432
• Main Authors: Forte, Stefano, Pagliuca, Alfredo, Maniscalchi, Eugenia T, Gulino, Rosario, Calabrese, Giovanna, Ricci-Vitiani, Lucia, Pallini, Roberto, Signore, Michele, Parenti, Rosalba, De Maria, Ruggero, Gulisano, Massimo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.12.2013; Public Library of Science (PLoS)
• Subjects: Adult; Aged; AKT protein; Analysis; Apoptosis; Astrocytoma; Brain; Brain cancer; Brain tumors; Cancer; Cancer therapies; Cell cycle; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell differentiation; Cell Differentiation - genetics; Cell Differentiation - physiology; Central nervous system; Chemotherapy; Deoxyribonucleic acid; Differentiation (biology); DNA; DNA methylation; DNA repair; Endopeptidases - genetics; Endopeptidases - metabolism; Epidermal growth factor; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Glioblastoma; Glioblastoma multiforme; Glioblastomas; Glioma; Hematology; Humans; Immunodeficiency; Male; Medical prognosis; Medicine; Middle Aged; Neoplastic Stem Cells - metabolism; Nervous system; Neurosurgery; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oncology; Phosphatase; Prognosis; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Proteins; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; PTEN protein; Rodents; Stem cell transplantation; Stem cells; Tumor cells; Tumor suppressor genes; Tumors; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0081432

The term astrocytoma defines a quite heterogeneous group of neoplastic diseases that collectively represent the most frequent brain tumors in humans. Among them, glioblastoma multiforme represents the most malignant form and its associated prognosis is one of the poorest among tumors of the central nervous system. It has been demonstrated that a small population of tumor cells, isolated from the brain neoplastic tissue, can reproduce the parental tumor when transplanted in immunodeficient mouse. These tumor initiating cells are supposed to be involved in cancer development and progression and possess stem cell-like features; like their normal counterpart, these cells remain quiescent until they are committed to differentiation. Many studies have shown that the role of the tumor suppressor protein PTEN in cell cycle progression is fundamental for tumor dynamics: in low grade gliomas, PTEN contributes to maintain cells in G1 while the loss of its activity is frequently observed in high grade gliomas. The mechanisms underlying the above described PTEN activity have been studied in many tumors, but those involved in the maintenance of tumor initiating cells quiescence remain to be investigated in more detail. The aim of the present study is to shed light on the role of PTEN pathway on cell cycle regulation in Glioblastoma stem cells, through a cell differentiation model. Our results suggest the existence of a molecular mechanism, that involves DUB3 and WEE1 gene products in the regulation of Cdc25a, as functional effector of the PTEN/Akt pathway.