Premium
Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV‐Cripto‐1 transgenic mice
Author(s) -
Strizzi Luigi,
Bianco Caterina,
Normanno Nicola,
Seno Masaharu,
Wechselberger Christian,
WallaceJones Brenda,
Khan Nadia I.,
Hirota Morihisa,
Sun Youping,
Sanicola Michele,
Salomon David S.
Publication year - 2004
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20062
Subject(s) - vimentin , epithelial–mesenchymal transition , cyclin d1 , biology , protein kinase b , microbiology and biotechnology , focal adhesion , mouse mammary tumor virus , cancer research , signal transduction , cell , cell cycle , immunohistochemistry , cancer , immunology , metastasis , virus , genetics
Epithelial‐mesenchymal transition (EMT) facilitates migration and invasion of epithelial tumor cells. Cripto‐1 (CR‐1), a member of the epidermal growth factor‐CFC protein family increases migration of cells in vitro. Here the expression of molecular markers and signaling molecules characteristic of EMT were assessed in mammary gland hyperplasias and tumors from mice expressing the human CR‐1 transgene by the MMTV promoter (MMTV‐CR‐1) and in mouse mammary epithelial cell line HC‐11 overexpressing CR‐1 (HC‐11/CR‐1). Western blot analysis showed decreased expression of E‐cadherin in MMTV‐CR‐1 tumors and in HC‐11/CR‐1 cells. The expression of N‐cadherin, vimentin, cyclin‐D1, and of the zinc‐finger transcription factor, snail, was increased in MMTV‐CR‐1 tumors. Increased snail mRNA was also found in HC‐11/CR‐1 cells. Expression of phosphorylated (P)‐c‐Src, P‐focal adhesion kinase (FAK), P‐Akt, P‐glycogen synthease kinase 3β (GSK‐3β), dephosphorylated (DP)‐β‐catenin, and various integrins such as, alpha 3, alpha v, beta 1, beta 3, and beta 4 was also increased in MMTV‐CR‐1 tumors. Immunohistochemistry showed positive staining for vimentin, N‐cadherin, cyclin‐D1, smooth muscle actin, fibronectin, snail, and β‐catenin in MMTV‐CR‐1 tumor sections. HC‐11/CR‐1 cells treated with the c‐Src inhibitor PP2 reduced the expression of P‐c‐Src and of P‐FAK, P‐Akt, P‐GSK‐3β, DP‐β‐catenin all known to be activated by c‐Src. Migration of HC‐11/CR‐1 cells was also reduced by PP2 treatment. These results suggest that CR‐1 may play a significant role in promoting the increased expression of markers and signaling molecules associated with EMT. © 2004 Wiley‐Liss, Inc.