Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 27, Issue 8, Pages 3165-3175Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.01315-06
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Funding
- NCI NIH HHS [P01 CA030195, P50 CA058183, P50CA58183, R01 CA094118, R01CA94118, P01CA30195] Funding Source: Medline
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Type I insulin-like growth factor receptor (IGF-IR) can transform mouse fibroblasts; however, little is known about the transforming potential of IGF-IR in human fibroblasts or epithelial cells. We found that overexpression of a constitutively activated IGF-IR (CD8-IGF-IR) was sufficient to cause transformation of immortalized human mammary epithelial cells and growth in immunocompromised mice. Furthermore, CD8-IGF-IR caused cells to undergo an epithelial-to-mesenchymal transition (EMT) which was associated with dramatically increased migration and invasion. The EMT was mediated by the induction of the transcriptional repressor Snail and downregulation of E-cadherin. NF-kappa B was highly active in CD8-IGF-IR-MCF10A cells, and both increased levels of Snail and the EMT were partially reversed by blocking NF-kappa B or IGF-IR activity. This study places IGF-IR among a small group of oncogenes that, when overexpressed alone, can confer in vivo tumorigenic growth of MCF10A cells and indicates the hierarchy in the mechanism of IGF-IR-induced EMT.
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