Genetic modulation of hypoxia induced gene expression and angiogenesis relevance to brain tumors

摘要: Angiogenesis is required for the development and biologic progression of infiltrative astrocytomas takes form "microvascular hyperplasia" in glioblastoma multiforme, most malignant astrocytoma. This pathologic term refers to an abnormal vascular proliferation that often associated with necrosis likely originates hypoxic zones. Both physiologic response hypoxia genetic alterations contribute this process. The presence regions within expanding tumor mass leads upregulation pro-angiogenic factors, such as endothelial growth factor (VEGF), through increased activity transcriptional complex HIF-1 (hypoxia-inducible factor-1). mediated gene expression may be directly or indirectly modulated by oncogenes/tumor suppressor genes occur during astrocytoma development, including PTEN, TP53, p16(CDKN2A), p14ARF, EGFR, PDGFR. Genetic are also believed influence HIF-independent pro- anti- angiogenic basic fibroblast (bFGF) thrombospondin-1 (TSP-1), respectively. Thus, events infiltrating promote angiogenesis, both modulating induced regulating factors.