HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Gene-linked shift in ganglioside distribution influences growth and vascularity in a mouse astrocytoma.

Abstract
Brain tumor growth and progression is dependent upon vascularity, and is associated with altered ganglioside composition and distribution. In this study, we examined the influence of gangliosides on growth and vascularity in a malignant mouse astrocytoma, CT-2A. Ganglioside distribution was altered in CT-2A tumor cells using an antisense construct to beta-1,4-N-acetylgalactosaminyltransferase (GalNAc-T), a key enzyme that uses the simple ganglioside GM3 as a substrate for the synthesis of the more complex gangliosides, GM2, GM1 and GD1a. GalNAc-T gene expression was significantly lower in CT-2A cells stably transfected with the antisense GalNAc-T plasmid, pcDNA3.1/TNG (CT-2A/TNG) than in either non-transfected CT-2A or mock-transfected (CT-2A/V) control tumor cells. GM3 was elevated from 16% to 58% of the total ganglioside distribution, whereas GM1 and GD1a were reduced from 17% and 49% to 10% and 17%, respectively, in CT-2A/TNG tumor cells. Growth, vascularity (blood vessel density and Matrigel assay) and vascular endothelial growth factor (VEGF) expression was significantly less in CT-2A/TNG tumors than in control CT-2A brain tumors. In addition, the expression of VEGF, hypoxia-inducible factor 1alpha (HIF-1alpha) and neuropilin-1 (NP-1) was significantly lower in CT-2A/TNG tumor cells than in control CT-2A tumor cells. These data suggest that gene-linked changes in ganglioside composition influence the growth and angiogenic properties of the CT-2A astrocytoma.
AuthorsLaura E Abate, Purna Mukherjee, Thomas N Seyfried
JournalJournal of neurochemistry (J Neurochem) Vol. 98 Issue 6 Pg. 1973-84 (Sep 2006) ISSN: 0022-3042 [Print] England
PMID16911584 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Gangliosides
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Oligonucleotides, Antisense
  • Vascular Endothelial Growth Factor A
  • Neuropilin-1
  • N-Acetylgalactosaminyltransferases
  • polypeptide N-acetylgalactosaminyltransferase
Topics
  • Animals
  • Astrocytoma (blood supply, genetics, metabolism, pathology)
  • Brain Neoplasms (blood supply, genetics, metabolism, pathology)
  • Cell Proliferation
  • Down-Regulation
  • Gangliosides (metabolism)
  • Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Mice, SCID
  • N-Acetylgalactosaminyltransferases (genetics, metabolism)
  • Neuropilin-1 (metabolism)
  • Oligonucleotides, Antisense (pharmacology)
  • Plasmids
  • Tissue Distribution (drug effects)
  • Transfection
  • Vascular Endothelial Growth Factor A (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: