Nickl-Jockschat, T. and Arslan, F. and Doerfelt, A. and Bogdahn, U. and Bosserhoff, A. and Hau, P. (2007) An imbalance between Smad and MAPK pathways is responsible for TGF-B tumor promoting effects in high-grade gliomas. INTERNATIONAL JOURNAL OF ONCOLOGY, 30 (2). pp. 499-507. ISSN 1019-6439,
Full text not available from this repository. (Request a copy)Abstract
The transforming growth factor-beta (TGF-beta) plays a pivotal role in the pathobiology of human gliomas: during carcinogenesis. it turns from a tumor suppressor to a tumor promoter. The traditional Smad pathway and the more recently discovered MAPK pathway are the most important pathways for TGF-beta related intracellular signal transduction mediating differential pathobiological effects. In this study, we investigated the effects of TGF-beta 2 and the TGF-beta 2 antisense phosphorothioate oligodeoxynucleotide (PTO) AS-11 on the functionality of both the Smad and MAPK pathways in high-grade gliomas. We aimed to correlate the imbalance between the pathways with differences in the behaviour of high-grade glioma cells. Gene and protein expression studies were used to detect levels of members of the Smad and MAPK pathways under regulation of TGF-beta 2 and AS-11. Proliferation and migration assays were functional readouts for effects caused by these regulating tools. Gene arrays were used to detect yet unknown regulators of these functional effects. The Smad pathway was functional in the tested cell lines. Exogenous TGF-beta 2 inhibited proliferation but enhanced migration. Smad 2 mRNA expression and activation were significantly reduced by incubation with AS-11. K-ras was reduced both in gene arrays and quPCR under treatment with AS-11, but there was no influence of K-ras down-regulation on the activity of ERK. Ubiquitination-related genes also were specifically downregulated with AS-11. Our results indicate the involvement of K-ras in TGF-beta signaling in high-grade gliomas. ERK, which is a member of the MAPK pathway, was not influenced and seems to be activated through RAS independent cascades in glioma. These results suggest that combined antagonization of the TGF-beta and MAPK pathways might be a promising approach for glioma therapy. An imbalance between these two pathways might be responsible for TGF-beta switching to a tumor promoter protein in high-grade gliomas.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; EPITHELIAL-CELLS; PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES; DISEASE PROGRESSION; PROTEIN EXPRESSION; SUPPRESSOR SMAD4; ONCOGENIC RAS; COLON-CANCER; RING FINGER; TGF-B; high-grade glioma; Smad pathway; MAPK pathway |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Dec 2020 10:59 |
| Last Modified: | 22 Dec 2020 10:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33238 |
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