Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Hoda, MA; Münzker, J; Ghanim, B; Schelch, K; Klikovits, T; Laszlo, V; Sahin, E; Bedeir, A; Lackner, A; Dome, B; Setinek, U; Filipits, M; Eisenbauer, M; Kenessey, I; Török, S; Garay, T; Hegedus, B; Catania, A; Taghavi, S; Klepetko, W; Berger, W; Grusch, M.
Suppression of activin A signals inhibits growth of malignant pleural mesothelioma cells.
Br J Cancer. 2012; 107(12):1978-1986
Doi: 10.1038/bjc.2012.519
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- Leading authors Med Uni Graz
- Münzker Julia
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- Abstract:
- Activins control the growth of several tumour types including thoracic malignancies. In the present study, we investigated their expression and function in malignant pleural mesothelioma (MPM). The expression of activins and activin receptors was analysed by quantitative PCR in a panel of MPM cell lines. Activin A expression was further analysed by immunohistochemistry in MPM tissue specimens (N=53). Subsequently, MPM cells were treated with activin A, activin receptor inhibitors or activin-targeting siRNA and the impact on cell viability, proliferation, migration and signalling was assessed. Concomitant expression of activin subunits and receptors was found in all cell lines, and activin A was overexpressed in most cell lines compared with non-malignant mesothelial cells. Similarly, immunohistochemistry demonstrated intense staining of tumour cells for activin A in a subset of patients. Treatment with activin A induced SMAD2 phosphorylation and stimulated clonogenic growth of mesothelioma cells. In contrast, treatment with kinase inhibitors of activin receptors (SB-431542, A-8301) inhibited MPM cell viability, clonogenicity and migration. Silencing of activin A expression by siRNA oligonucleotides further confirmed these results and led to reduced cyclin D1/3 expression. Our study suggests that activin A contributes to the malignant phenotype of MPM cells via regulation of cyclin D and may represent a valuable candidate for therapeutic interference.
- Find related publications in this database (using NLM MeSH Indexing)
- Activins - antagonists & inhibitors
- Antineoplastic Agents - pharmacology
- Blotting, Western -
- Cell Movement -
- Cell Proliferation -
- Cell Survival -
- Cyclin D - drug effects
- Cyclin D - metabolism
- Gene Expression Regulation, Neoplastic -
- Gene Silencing -
- Humans -
- Immunohistochemistry -
- Mesothelioma - drug therapy
- Mesothelioma - metabolism
- Mesothelioma - pathology
- Phenotype -
- Phosphorylation - drug effects
- Pleural Neoplasms - drug therapy
- Pleural Neoplasms - metabolism
- Pleural Neoplasms - pathology
- RNA, Small Interfering - pharmacology
- Real-Time Polymerase Chain Reaction -
- Signal Transduction - drug effects
- Smad2 Protein - metabolism
- Tumor Stem Cell Assay -
- Up-Regulation -
- Find related publications in this database (Keywords)
- mesothelioma
- activin
- activin receptor
- SMAD signalling
- targeted therapy