Abstract
Epithelial-mesenchymal transition (EMT) is a process occurring during both embryogenesis and early stages of invasive cancer. Epithelial cells that undergo EMT become more migratory and invasive with a mesenchymal morphology. Herein we assess EMT induction in a mouse mammary epithelial cell line driven by Msx2, a homeobox-containing transcription factor important during mammary gland development. NMuMG cells, a normal mouse mammary epithelial cell line, stably transfected with a Msx2 cDNA showed downregulation of an epithelial marker E-cadherin and upregulation of the mesenchymal markers vimentin and N-cadherin. Furthermore, overexpression of Cripto-1, a member of the epidermal growth factor-CFC protein family already known to be involved in EMT, was detected in Msx2-transfected cells. The expression of Cripto-1 was accompanied by activation of the tyrosine kinase c-Src pathway and an increase in the invasive ability of the cells. Functional assays also demonstrated inhibition of the invasive behavior of the Msx2-transfected cells by a c-Src specific inhibitor. Moreover, immunohistochemistry of human infiltrating breast carcinomas showed positive staining for Msx2 only in the infiltrating tumor cells while the non-infiltrating tumor cells were negative. These results suggest that Msx2 may play a significant role in promoting EMT in epithelial cells that acquire properties involved in tumor invasion. J. Cell. Physiol. 219: 659-666, 2009. Published 2009 Wiley-Liss, Inc.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, N.I.H., Intramural
MeSH terms
-
Animals
-
Base Sequence
-
Breast Neoplasms / genetics
-
Breast Neoplasms / metabolism
-
Breast Neoplasms / pathology
-
CSK Tyrosine-Protein Kinase
-
Carcinoma, Ductal, Breast / genetics
-
Carcinoma, Ductal, Breast / metabolism
-
Carcinoma, Ductal, Breast / pathology
-
Cell Line
-
DNA Primers / genetics
-
Epidermal Growth Factor / antagonists & inhibitors
-
Epidermal Growth Factor / genetics
-
Epidermal Growth Factor / metabolism*
-
Epithelial Cells / cytology
-
Epithelial Cells / metabolism
-
Female
-
Homeodomain Proteins / genetics
-
Homeodomain Proteins / metabolism*
-
Humans
-
Mammary Glands, Animal / cytology*
-
Mammary Glands, Animal / growth & development
-
Mammary Glands, Animal / metabolism*
-
Membrane Glycoproteins / antagonists & inhibitors
-
Membrane Glycoproteins / genetics
-
Membrane Glycoproteins / metabolism*
-
Mesoderm / cytology
-
Mesoderm / metabolism
-
Mice
-
Neoplasm Invasiveness / genetics
-
Neoplasm Invasiveness / pathology
-
Neoplasm Invasiveness / physiopathology
-
Neoplasm Proteins / antagonists & inhibitors
-
Neoplasm Proteins / genetics
-
Neoplasm Proteins / metabolism*
-
Protein-Tyrosine Kinases / metabolism
-
RNA, Small Interfering / genetics
-
Recombinant Proteins / genetics
-
Recombinant Proteins / metabolism
-
Signal Transduction
-
Transfection
-
Up-Regulation
-
src-Family Kinases
Substances
-
DNA Primers
-
Homeodomain Proteins
-
MSX2 protein
-
Membrane Glycoproteins
-
Neoplasm Proteins
-
RNA, Small Interfering
-
Recombinant Proteins
-
Tdgf1 protein, mouse
-
Epidermal Growth Factor
-
Protein-Tyrosine Kinases
-
CSK Tyrosine-Protein Kinase
-
src-Family Kinases
-
CSK protein, human