Insulin-IGF signaling affects cell transformation in the BALB/c 3T3 cell model
| Autor: | Josefine Barbara Boerner, Michael Ristow, Luisa Szimmtenings, René Thierbach, Doerte Poburski, Christiane Leovsky, Michael Glei |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Tumour-suppressor proteins Targeted therapies Mechanisms of disease Cancer models Linsitinib BALB 3T3 Cells MAP Kinase Signaling System Cell Article Receptor IGF Type 1 03 medical and health sciences chemistry.chemical_compound Mice Somatomedins medicine Animals Insulin Mode of action Receptor Multidisciplinary Mitogen-Activated Protein Kinase 3 Chemistry Cell growth Receptor Insulin Cell biology Neoplasm Proteins 030104 developmental biology medicine.anatomical_structure Cell Transformation Neoplastic Diabetes Mellitus Type 2 Phosphorylation |
| Zdroj: | Scientific Reports Scientific Reports, 6 |
| ISSN: | 2045-2322 |
| DOI: | 10.3929/ethz-b-000122778 |
| Popis: | The increased cancer mortality of diabetes type 2 patients is most likely an evidence of the tight connection between tumor development and energy metabolism. A major focus of today’s research is still the identification of key proteins of both diseases and the development of corresponding inhibitors. In this study we combined the two-stage BALB/c-3T3 cell transformation assay (BALB-CTA) with the IR/IGF-1R inhibitor OSI-906 (linsitinib) and analyzed alterations in protein activity and energy parameters in non-transformed as well as transformed cells. OSI-906 successfully inhibited the phosphorylation of IR/IGF-1R and decreased cell growth in non-transformed cells. In the BALB-CTA, a permanent treatment with OSI-906 reduced cellular transformation dose-dependently, whereas a temporary treatment gave evidence for a preventive effect in the promotion phase. Furthermore, even though several key proteins were affected, it was possible to show that the phosphorylation of GSK3, Erk 1/2 and the S6 protein are not crucial for the cell foci reducing effect of OSI-906. Taken together, the BALB-CTA confirmed results of OSI-906 from animal studies and enhanced the knowledge of its mode of action. Therefore, the BALB-CTA offers the opportunity to analyze alterations in the transformation process more precisely and will be helpful to identify effective cancer treatments. Scientific Reports, 6 ISSN:2045-2322 |
| Databáze: | OpenAIRE |
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