Anchorage-independent growth of fibroblasts that express a truncated IGF-I receptor.
The purpose of this investigation was to study signaling by an insulin-like growth factor I receptor (IGF-I R) that lacks the extracellular portion of the receptor. We transfected IGF-I R-negative mouse embryo fibroblasts with a truncated IGF-I R consisting of only the transmembrane and cytoplasmic part of the beta subunit. Proliferation as assessed by counting cells was the same for vector only transfectants and the truncated receptor transfectants in defined medium containing EGF and PDGF. In contrast, anchorage-independent growth as measured by colony formation in soft agar was markedly increased for the truncated IGF-I R transfectants compared to the vector transfectants. MAP-kinase activity in the truncated IGF-I R transfectants was not higher than in the vector transfectants; however, PI 3-kinase activity was significantly higher in the IGF-I R transfectants. These results provide evidence that an IGF-I receptor consisting of only the transmembrane and cytoplasmic domain of the beta subunit can signal pathways leading to anchorage-independent growth.
Himmelmann
B
B
Endocrinology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Terry
C
C
Dey
B R
BR
Lopaczynski
W
W
Nissley
P
P
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D015398:Signal Transduction; D014162:Transfection
D016895:Culture Media, Serum-Free; D010982:Platelet-Derived Growth Factor; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D019950:Mitogen-Activated Protein Kinase 1