title: Insulin-IGF signaling affects cell transformation in the BALB/c 3T3 cell model.
abstract: 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.
authors.affiliation: Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Str. 24, 07743 Jena, Germany.
authors.forename: Doerte
authors.initials: D
authors.lastname: Poburski
authors.affiliation: Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Str. 24, 07743 Jena, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Leovsky
authors.affiliation: Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Str. 24, 07743 Jena, Germany.
authors.forename: Josefine Barbara
authors.initials: JB
authors.lastname: Boerner
authors.affiliation: Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Str. 24, 07743 Jena, Germany.
authors.forename: Luisa
authors.initials: L
authors.lastname: Szimmtenings
authors.affiliation: Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Str. 24, 07743 Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ristow
authors.affiliation: Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Str. 24, 07743 Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Glei
authors.affiliation: Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Str. 24, 07743 Jena, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Thierbach
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*; D013002:Somatomedins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D009363:Neoplasm Proteins; D013002:Somatomedins; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D048052:Mitogen-Activated Protein Kinase 3