Inducible dimerization of FGFR1 : development of a mouse model to analyze progressive transformation of the mammary gland (original) (raw)
Article| May 13 2002
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030
2Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030
Search for other works by this author on:
2Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030
3Department of Immunology, Baylor College of Medicine, Houston, TX 77030
Search for other works by this author on:
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030
Search for other works by this author on:
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030
Search for other works by this author on:
2Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030
3Department of Immunology, Baylor College of Medicine, Houston, TX 77030
Search for other works by this author on:
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030
2Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030
Search for other works by this author on:
Bryan E. Welm
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030
2Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030
Kevin W. Freeman
2Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030
3Department of Immunology, Baylor College of Medicine, Houston, TX 77030
Mercy Chen
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030
Alejandro Contreras
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030
David M. Spencer
2Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030
3Department of Immunology, Baylor College of Medicine, Houston, TX 77030
Jeffrey M. Rosen
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030
2Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030
Address correspondence to J.M. Rosen, Dept. of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Tel.: 713-798-6210. Fax: 713-798-8012. E-mail: [email protected]
The online version of this article contains supplemental material.
B.E. Welm's present address is Dept. of Anatomy, University of California, San Francisco, San Francisco, CA 94143.
Abbreviations used in this paper: BrdU, 5-bromo-2′-deoxyuridine; ECM, extracellular matrix; FGF, fibroblast growth factor; FGFR, FGF receptor; H&E, hematoxylin and eosin; HA, hemagglutinin; LTR, long terminal repeat; MAPK, mitogen-activated protein kinase; MMP, matrix metalloproteinase; MMTV, mouse mammary tumor virus; PR, progesterone receptor; TEB, terminal-end bud; TUNEL, TdT-mediated dUTP-biotin nick end labeling.
Received: July 27 2001
Revision Received: March 22 2002
Accepted: March 22 2002
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2002
J Cell Biol (2002) 157 (4): 703–714.
To develop an inducible and progressive model of mammary gland tumorigenesis, transgenic mice were generated with a mouse mammary tumor virus–long terminal repeat–driven, conditional, fibroblast growth factor (FGF)–independent FGF receptor (FGFR)1 (iFGFR1) that can be induced to dimerize with the drug AP20187. Treatment of transgenic mice with AP20187 resulted in iFGFR1 tyrosine phosphorylation, increased proliferation, activation of mitogen-activated protein kinase and Akt, and lateral budding. Lateral buds appeared as early as 3 d after AP20187 treatment and initially consisted of bilayered epithelial cells and displayed apical and basolateral polarity appeared after 13 d of AP20187 treatment. Invasive lesions characterized by multicell-layered lateral buds, decreased myoepithelium, increased vascular branching, and loss of cell polarity were observed after 2–4 wk of treatment. These data indicate that acute iFGFR1 signaling results in increased lateral budding of the mammary ductal epithelium, and that sustained activation induces alveolar hyperplasia and invasive lesions.
The Rockefeller University Press
2002
You do not currently have access to this content.
Sign in
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Username (Note: This may be your email address.) ?
Password
Could not validate captcha. Please try again.
12,437 Views
121 Web of Science