A functional insulin-like growth factor I receptor is required for the mitogenic and transforming activities of the epidermal growth factor receptor.
Open Access
- 1 July 1994
- journal article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 14 (7) , 4588-4595
- https://doi.org/10.1128/mcb.14.7.4588
Abstract
When wild-type mouse embryo cells are stably transfected with a plasmid constitutively overexpressing the epidermal growth factor (EGF) receptor (EGFR), the resulting cells can grow in serum-free medium supplemented solely with EGF. Supplementation with EGF also induces in these cells the transformed phenotype (growth in soft agar). However, when the same EGFR expression plasmid is introduced and overexpressed in cells derived from littermate embryos in which the insulin-like growth factor I (IGF-I) receptor genes have been disrupted by homologous recombination, the resulting cells are unable to grow or to be transformed by the addition of EGF. Reintroduction into these cells (null for the IGF-I receptor) of a wild-type (but not of a mutant) IGF-I receptor restores EGF-mediated growth and transformation. Our results indicate that at least in mouse embryo fibroblasts, the EGFR requires the presence of a functional IGF-I receptor for its mitogenic and transforming activities.Keywords
This publication has 59 references indexed in Scilit:
- Ras-Independent Growth Factor Signaling by Transcription Factor Tyrosine PhosphorylationScience, 1993
- How receptors turn Ras onNature, 1993
- Grb2 mediates the EGF-dependent activation of guanine nucleotide exchange on RasNature, 1993
- Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signallingNature, 1993
- The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1Nature, 1993
- Interference of the IGF system as a strategy to inhibit breast cancer growthBreast Cancer Research and Treatment, 1992
- Myc rescue of a mutant CSF-1 receptor impaired in mitogenic signallingNature, 1991
- Characterization of the growth of murine fibroblasts that express human insulin receptorsExperimental Cell Research, 1990
- Blockade of the type I somatomedin receptor inhibits growth of human breast cancer cells in athymic mice.Journal of Clinical Investigation, 1989
- Platelet-derived growth factor and the regulation of the mammalian fibroblast cell cycleBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1979