Insulin action on H292 bronchial carcinoma cells as compared to normal bronchial epithelial cells.
Inhaled insulin may contribute to bronchial carcinoma due to IGF-I receptor activation by high local concentrations. Therefore, effects of insulin and IGF-I on human bronchial carcinoma cells (H292) and normal bronchial epithelium cells (HBE) were studied. TGF-β was included since it also influences carcinoma progression. H292 and HBE cells expressed both the insulin receptor and the IGF-I receptor; in H292 cells an additional, shorter, splicing variant (IR-A) of the insulin receptor was present. Insulin receptor expression was around four to five times higher in H292 than in HBE cells at mRNA and protein levels. Insulin and TGF-β exerted contrary actions on proliferation and gene expression in H292 cells. Genes regulated by insulin, IGF-I, and TGF-β were linked to inflammation, cell adhesion, muscle contraction and differentiation. Insulin and IGF-I also suppressed DNA repair genes. EC(50) for insulin-induced proliferation was around 5 nM in H292 and around 30 nM HBE cells. The EC(50) values for gene expression ranged from 9 to 90 nM in both cell types, dependent on the gene studied. In H292 cells, the proliferative response was much stronger if TGF-β was present. In HBE cells this interaction of insulin and TGF-β was not observed, and changes in gene expression were mostly lower by at least 10-fold as compared to H292. All in all, the insulin effects in H292 were generally much stronger than in HBE cells and - with regard to proliferation - occurred at lower concentrations. Thus, insulin will hardly induce cancer from normal bronchial cells but may favour progression of pre-existing tumours.
Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, D-53175 Bonn, Germany. pmayer@bfarm.de
Peter
P
Mayer
Ulrich
U
Reitzenstein
Mareille
M
Warnken
Harald
H
Enzmann
Kurt
K
Racké
D000280:Administration, Inhalation; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000187:drug effects*; D001984:Bronchial Neoplasms / Q000473:pathology*; D002277:Carcinoma / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017931:DNA Primers; D004847:Epithelial Cells / Q000187:drug effects*; D005786:Gene Expression Regulation; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017403:In Situ Hybridization; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D016133:Polymerase Chain Reaction; D011972:Receptor, Insulin / Q000096:biosynthesis; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology
D017931:DNA Primers; D007004:Hypoglycemic Agents; D007328:Insulin; D016212:Transforming Growth Factor beta; D011972:Receptor, Insulin; D013936:Thymidine