Tumor hypoxia: Impact on gene amplification in glioblastoma
- PMID: 18695880
Tumor hypoxia: Impact on gene amplification in glioblastoma
Abstract
Gene amplification is frequently found in human glioblastoma but the mechanisms driving amplifications remain to be elucidated. Hypoxia as hallmark of glioblastoma is known to be involved in the induction of fragile sites that are central to gene amplification. We analyzed the potential of hypoxia (pO2 0%) and mini hypoxia (pO2 5%) to induce fragile sites within a homogeneously staining region (HSR) at 12q14-15 in a glioblastoma cell line (TX3868). Treatment of cells by hypoxia or by mini hypoxia induced double minutes (DMs) and caused breakage of the HSR structure at 12q14-15, suggesting a novel hypoxia inducible fragile site on 12q. Treatment with aphidicolin, a known fragile site inducer, indicates that the hypoxia inducible fragile site is a common fragile site. Reintegration of amplified sequences and occurrence of anaphase-bridge-like structures shows that mini hypoxia and hypoxia are able to initiate amplification processes in human glioblastoma cells. Hypoxia as known tumor microenvironment factor is crucial for the development of amplifications in glioblastoma. The identification and characterization of novel common fragile sites induced by hypoxia will improve the understanding of mechanisms underlying amplifications in glioblastoma.
Similar articles
-
Induction of multiple double-strand breaks within an hsr by meganucleaseI-SceI expression or fragile site activation leads to formation of double minutes and other chromosomal rearrangements.Oncogene. 2002 Oct 31;21(50):7671-9. doi: 10.1038/sj.onc.1205880. Oncogene. 2002. PMID: 12400009
-
Novel aphidicolin-inducible common fragile site FRA9G maps to 9p22.2, within the C9orf39 gene.Genes Chromosomes Cancer. 2007 Nov;46(11):991-9. doi: 10.1002/gcc.20484. Genes Chromosomes Cancer. 2007. PMID: 17668870
-
When, where and how the bridge breaks: anaphase bridge breakage plays a crucial role in gene amplification and HSR generation.Exp Cell Res. 2005 Jan 15;302(2):233-43. doi: 10.1016/j.yexcr.2004.09.001. Exp Cell Res. 2005. PMID: 15561104
-
Manifestation, mechanisms and mysteries of gene amplifications.Cancer Lett. 2006 Jan 28;232(1):79-89. doi: 10.1016/j.canlet.2005.07.045. Epub 2005 Nov 8. Cancer Lett. 2006. PMID: 16288831 Review.
-
The molecular basis of common and rare fragile sites.Cancer Lett. 2006 Jan 28;232(1):13-26. doi: 10.1016/j.canlet.2005.07.039. Epub 2005 Oct 19. Cancer Lett. 2006. PMID: 16236432 Review.
Cited by
-
Cancer Stem Cells: Significance in Origin, Pathogenesis and Treatment of Glioblastoma.Cells. 2021 Mar 11;10(3):621. doi: 10.3390/cells10030621. Cells. 2021. PMID: 33799798 Free PMC article. Review.
-
SUMO and cellular adaptive mechanisms.Exp Mol Med. 2020 Jun;52(6):931-939. doi: 10.1038/s12276-020-0457-2. Epub 2020 Jun 26. Exp Mol Med. 2020. PMID: 32591648 Free PMC article. Review.
-
Multifaceted control of DNA repair pathways by the hypoxic tumor microenvironment.DNA Repair (Amst). 2015 Aug;32:180-189. doi: 10.1016/j.dnarep.2015.04.030. Epub 2015 May 1. DNA Repair (Amst). 2015. PMID: 25956861 Free PMC article. Review.
-
Involvement of Thyroid Hormones in Brain Development and Cancer.Cancers (Basel). 2021 May 30;13(11):2693. doi: 10.3390/cancers13112693. Cancers (Basel). 2021. PMID: 34070729 Free PMC article. Review.
-
Brain tumor hypoxia: tumorigenesis, angiogenesis, imaging, pseudoprogression, and as a therapeutic target.J Neurooncol. 2009 May;92(3):317-35. doi: 10.1007/s11060-009-9827-2. Epub 2009 Apr 9. J Neurooncol. 2009. PMID: 19357959 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
