Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Arzt, L; Kothmaier, H; Halbwedl, I; Quehenberger, F; Popper, HH.
Signal transducer and activator of transcription 1 (STAT1) acts like an oncogene in malignant pleural mesothelioma.
Virchows Arch. 2014; 465(1):79-88
Doi: 10.1007/s00428-014-1584-8
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Arzt-Gradwohl Lisa
- Co-Autor*innen der Med Uni Graz
- Halbwedl Iris
- Kothmaier Hannelore
- Popper Helmuth
- Quehenberger Franz
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- Abstract:
- Malignant pleural mesothelioma (MPM) is the most common primary tumor of the pleura. Its incidence is increasing in Europe and the prognosis remains poor. We compared epithelioid MPM in short and long survivors, and identified signal transducer and activator of transcription 1 (STAT1) as probably being responsible for antiapoptotic signaling and chemoresistance. Six mesothelioma cell lines were evaluated by Western Blot. We also analyzed 16 epithelioid MPM tissue samples for the phosphorylation status of STAT1 and the expression of its negative regulator, the suppressor of cytokine signaling 1 (SOCS1). Formalin-fixed and paraffin-embedded tissue specimens were evaluated by protein-lysate microarray and immunohistochemistry. We found STAT1 to be highly expressed and STAT3 downregulated in MPM cell lines. The expression of STAT1 phosphorylated on tyrosine 701 (Y701) was increased by interferon-gamma (IFN-γ) treatment, whereas SOCS1 was not expressed. The expression of STAT1 phosphorylated on serine 727 (S727) was not detected in mesothelioma cell lines and was not stimulated by IFN-γ. STAT1 was phosphorylated on tyrosine 701 and serine 727 in MPM tissue samples. The expression of pSTAT1-Y701 was increased compared to pSTAT1-S727. SOCS1 was again not detectable. STAT1 is upregulated in MPM, and its action may be prolonged by a loss of the negative regulator SOCS1. STAT1 might, therefore, be a target for therapeutic intervention, with the intention to restore apoptotic mechanisms and sensitivity to chemotherapy. However, other regulatory mechanisms need to be investigated to clarify if lack of expression of SOCS1 is the only reason for sustained STAT1 expression in MPM.
- Find related publications in this database (using NLM MeSH Indexing)
- Cell Line, Tumor -
- Humans -
- Interferon-gamma - therapeutic use
- Lung Neoplasms - etiology Lung Neoplasms - physiopathology
- Mesothelioma - etiology Mesothelioma - physiopathology
- Oncogenes -
- Phosphorylation -
- STAT1 Transcription Factor - metabolism
- STAT3 Transcription Factor - metabolism
- Signal Transduction - genetics
- Suppressor of Cytokine Signaling Proteins - deficiency
- Up-Regulation -
- Find related publications in this database (Keywords)
- Interferon-gamma
- Malignant pleural mesothelioma
- Phosphorylated STAT1
- SOCS1
- STAT signaling