Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV-Cripto-1 transgenic mice

Luigi Strizzi, Caterina Bianco, Nicola Normanno, Masaharu Seno, Christian Wechselberger, Brenda Wallace-Jones, Nadia I. Khan, Morihisa Hirota, Youping Sun, Michele Sanicola, David S. Salomon

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)266-276
Number of pages11
JournalJournal of Cellular Physiology
Volume201
Issue number2
DOIs
Publication statusPublished - Nov 2004

Fingerprint

Epithelial-Mesenchymal Transition
Human Mammary Glands
Transgenic Mice
Hyperplasia
Tumors
Catenins
Cadherins
Focal Adhesion Protein-Tyrosine Kinases
Cyclin D1
Snails
Vimentin
Neoplasms
Glycogen
Phosphotransferases
Epithelial Cells
Cells
Zinc Fingers
Chlorofluorocarbons
Molecules
Transgenes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV-Cripto-1 transgenic mice. / Strizzi, Luigi; Bianco, Caterina; Normanno, Nicola; Seno, Masaharu; Wechselberger, Christian; Wallace-Jones, Brenda; Khan, Nadia I.; Hirota, Morihisa; Sun, Youping; Sanicola, Michele; Salomon, David S.

In: Journal of Cellular Physiology, Vol. 201, No. 2, 11.2004, p. 266-276.

Research output: Contribution to journalArticle

Strizzi, L, Bianco, C, Normanno, N, Seno, M, Wechselberger, C, Wallace-Jones, B, Khan, NI, Hirota, M, Sun, Y, Sanicola, M & Salomon, DS 2004, 'Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV-Cripto-1 transgenic mice', Journal of Cellular Physiology, vol. 201, no. 2, pp. 266-276. https://doi.org/10.1002/jcp.20062
Strizzi, Luigi ; Bianco, Caterina ; Normanno, Nicola ; Seno, Masaharu ; Wechselberger, Christian ; Wallace-Jones, Brenda ; Khan, Nadia I. ; Hirota, Morihisa ; Sun, Youping ; Sanicola, Michele ; Salomon, David S. / Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV-Cripto-1 transgenic mice. In: Journal of Cellular Physiology. 2004 ; Vol. 201, No. 2. pp. 266-276.
@article{a0f30353ea9c4627b403662e742f4b9b,
title = "Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV-Cripto-1 transgenic mice",
abstract = "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.",
author = "Luigi Strizzi and Caterina Bianco and Nicola Normanno and Masaharu Seno and Christian Wechselberger and Brenda Wallace-Jones and Khan, {Nadia I.} and Morihisa Hirota and Youping Sun and Michele Sanicola and Salomon, {David S.}",
year = "2004",
month = "11",
doi = "10.1002/jcp.20062",
language = "English",
volume = "201",
pages = "266--276",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Epithelial mesenchymal transition is a characteristic of hyperplasias and tumors in mammary gland from MMTV-Cripto-1 transgenic mice

AU - Strizzi, Luigi

AU - Bianco, Caterina

AU - Normanno, Nicola

AU - Seno, Masaharu

AU - Wechselberger, Christian

AU - Wallace-Jones, Brenda

AU - Khan, Nadia I.

AU - Hirota, Morihisa

AU - Sun, Youping

AU - Sanicola, Michele

AU - Salomon, David S.

PY - 2004/11

Y1 - 2004/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=4644300725&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4644300725&partnerID=8YFLogxK

U2 - 10.1002/jcp.20062

DO - 10.1002/jcp.20062

M3 - Article

C2 - 15334661

AN - SCOPUS:4644300725

VL - 201

SP - 266

EP - 276

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 2

ER -