Msx2 induces epithelial‐mesenchymal transition in mouse mammary epithelial cells through upregulation of Cripto‐1

Journal of Cellular Physiology - Tập 219 Số 3 - Trang 659-666 - 2009
M.G. di Bari1, Erika Ginsburg2, Joshua Plant2, Luigi Strizzi2, David S. Salomon2, Barbara K. Vonderhaar3
1Molecular and Cellular Endocrinology Section, Mammary Biology and Tumorigenesis Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
2Molecular and Cellular Endocrinology Section, Mammary Biology and Tumorigenesis Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
3Molecular and Cellular Endocrinology Section, Mammary Biology and Tumorigenesis Laboratory, Bldg 37 Room 1106A1, 37 Convent Drive, National Institutes of Health, Bethesda, MD 20892‐4254.

Tóm tắt

AbstractEpithelial‐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.

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Thông tin xuất bản

Journal of Cellular Physiology

Tập 219 Số 3

659-666

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