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SHR Neuro Krebs Kardio Lipid

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 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Münzker Julia
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Number of Figures: 6
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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
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