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New deals on the transcriptional and post-transcriptional regulation of TRP channel target genes during the angiogenesis of glioma.
- Source :
-
Journal of Experimental & Integrative Medicine . 2011, Vol. 1 Issue 4, p221-234. 14p. - Publication Year :
- 2011
-
Abstract
- Tumor angiogenesis isn't only the result of physiological adaptation to hypoxia in response to an increasing tumor mass, but it is also the result of critical genetic mutations that activate a transcriptional program for angiogenesis. Calcium (Ca2+) is an important second messenger and its entry through plasma membrane affects angiogenesis. Several reports indicate that Ca2+ permeable transient receptor potential (TRP) channels belonging to the TRPC, TRPV and TRPM represent target genes, down-stream to Notch1, PTEN, NFAT and Hif-1 transcriptional factors are activated during tumor angiogenesis. Several reports indicate that angiogenic growth factors such as vascular endothelial growth factor (VEGF) and basic firoblast growth factor (bFGF) may activate TRP channels at transcriptional and post-transcriptional levels, causing a subsequent rise in endothelial [Ca2+]i, which modulates signal transduction pathways regulating the angiogenesis. Conversely, Ca2+ influx through TRP channel activation may stimulate endothelial cells to trigger transcription, production and release of angiogenic growth factors such as VEGF and platelet-derived growth factor (PDGF) that stimulate angiogenesis. Thus for example, hypoxia by inducing Notch1 activation, increases the expression of a member of TRPC family, TRPC6 and induces [Ca2+]i that is coupled to activation of calcineurin-NFAT pathway that results in glioma angiogenesis. TRP channels might be a promising target for new therapeutic agents to anti-angiogenic therapy. However, we are only at the beginning to considering endothelial TRP channels as targets for novel anti-angiogenic therapeutic intervention. Further studies on the role of the different members of this ion channel family in physiology and pathology are required to understand the involvement of TRP channels in glioma angiogenesis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13094572
- Volume :
- 1
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Journal of Experimental & Integrative Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 84432423
- Full Text :
- https://doi.org/10.5455/jeim.290711.ir.006