Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-24068

Gramatzki, D; Pantazis, G; Schittenhelm, J; Tabatabai, G; Köhle, C; Wick, W; Schwarz, M; Weller, M; Tritschler, I (2009). Aryl hydrocarbon receptor inhibition downregulates the TGF-beta/Smad pathway in human glioblastoma cells. Oncogene, 28(28):2593-2605.

[img] PDF - Registered users only
1MB

Abstract

The dioxin/aryl hydrocarbon receptor (AhR) is a transcription factor, which has been attributed a role in human cancerogenesis, cell cycle progression and transforming growth factor-beta (TGF-beta) signaling. As TGF-beta is an important mediator of the malignant phenotype of human gliomas, we studied AhR expression and function in glioma cells. AhR was not only expressed in glioma cells in vitro, but was also detected in human gliomas in vivo by immunohistochemistry, with a predominantly nuclear staining in glioblastomas. The AhR agonist, 3-methylcholanthrene, induced AhR nuclear translocation and upregulated mRNA levels of the AhR target gene, cytochrome P450 1A1 (CYP1A1). Conversely, pharmacological inhibition of AhR using the novel AhR antagonist, CH-223191, or AhR gene silencing using small interfering RNA showed that constitutive AhR activity positively controls TGF-beta1, TGF-beta2 and latent TGF-beta-binding protein-1 protein levels in malignant glioma cells. Moreover, antagonism of AhR reduced clonogenic survival and invasiveness of glioma cells. In contrast, AhR regulates TGF-beta signaling negatively in non-neoplastic astrocytes. Thus, the pathogenesis of glioma formation may involve altered AhR regulation of the TGF-beta/Smad pathway, and AhR may represent a promising target for the treatment of human malignant gliomas and other diseases associated with pathological TGF-beta activity.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
DDC:610 Medicine & health
Language:English
Date:2009
Deposited On:17 Nov 2009 07:56
Last Modified:27 Nov 2013 19:17
Publisher:Nature Publishing Group
ISSN:0950-9232
Publisher DOI:10.1038/onc.2009.104
PubMed ID:19465936
Citations:Web of Science®. Times Cited: 20
Google Scholar™
Scopus®. Citation Count: 23

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page