Constitutively Active Type I Insulin-like Growth Factor Receptor Causes Transformation and Xenograft Growth of Immortalized Mammary Epithelial Cells and is Accompanied by an Epithelial-to-mesenchymal Transition Mediated by Nf-kappab and Snail.
From: Baylor College of Medicine, Breast Center MS:600, One Baylor Plaza, Room N1110, Houston, TX 77030, USA.
Molecular and cellular biology
- Publish Date: Apr 2007
- ISSN: 0270-7306
- Volume: 27
- Issue: 8
- Pages: 3165-75
- Medium: Print
- Language: English
- Citation (JAMA): Kim Hyun-Jung, Litzenburger Beate C, Cui Xiaojiang, et al. Constitutively Active Type I Insulin-like Growth Factor Receptor Causes Transformation and Xenograft Growth of Immortalized Mammary Epithelial Cells and is Accompanied by an Epithelial-to-mesenchymal Transition Mediated by Nf-kappab and Snail.. Mol. Cell. Biol. Apr 2007;27:3165-75
Abstract
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-kappaB was highly active in CD8-IGF-IR-MCF10A cells, and both increased levels of Snail and the EMT were partially reversed by blocking NF-kappaB 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.
Mesh Headings (Keywords): Animals, Antigens, CD8, Benzimidazoles, Cadherins, Cell Transformation, Neoplastic, Collagen, Down-Regulation, Drug Combinations, Epithelial Cells, Genes, Regulator, Humans, Laminin, Mammary Glands, Human, Mesoderm, Mice, Models, Biological, Morphogenesis, NF-kappa B, Proteoglycans, Pyridones, Receptor, IGF Type 1, Recombinant Fusion Proteins, Transcription Factors, Transplantation, Heterologous
Check for Full Text / PubMed Unique Identifier (PMID): 17296734
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