|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online 26 September 2007
doi: 10.1242/dev.008250
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department of Cell Biology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
* Author for correspondence (e-mail: rserra{at}uab.edu)
Accepted 20 August 2007
Transforming growth factor-ß (TGF-ß) plays an essential role in growth and patterning of the mammary gland, and alterations in its signaling have been shown to illicit biphasic effects on tumor progression and metastasis. We demonstrate in mice that TGF-ß (Tgfß) regulates the expression of a non-canonical signaling member of the wingless-related protein family, Wnt5a. Loss of Wnt5a expression has been associated with poor prognosis in breast cancer patients; however, data are lacking with regard to a functional role for Wnt5a in mammary gland development. We show that Wnt5a is capable of inhibiting ductal extension and lateral branching in the mammary gland. Furthermore, Wnt5a-/- mammary tissue exhibits an accelerated developmental capacity compared with wild-type tissue, marked by larger terminal end buds, rapid ductal elongation, increased lateral branching and increased proliferation. Additionally, dominant-negative interference of TGF-ß signaling impacts not only the expression of Wnt5a, but also the phosphorylation of discoidin domain receptor 1 (Ddr1), a receptor for collagen and downstream target of Wnt5a implicated in cell adhesion/migration. Lastly, we show that Wnt5a is required for TGF-ß-mediated inhibition of ductal extension in vivo and branching in culture. This study is the first to show a requirement for Wnt5a in normal mammary development and its functional connection to TGF-ß.
Key words: Wnt5a, Mammary gland, TGF-ß, Ddr1, Non-canonical Wnt, Mouse
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  V. Jenei, V. Sherwood, J. Howlin, R. Linnskog, A. Safholm, L. Axelsson, and T. Andersson A t-butyloxycarbonyl-modified Wnt5a-derived hexapeptide functions as a potent antagonist of Wnt5a-dependent melanoma cell invasion PNAS, November 17, 2009; 106(46): 19473 - 19478. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Hansen, J. Howlin, A. Tengholm, O. Dyachok, W. F. Vogel, A. C. Nairn, P. Greengard, and T. Andersson Wnt-5a-induced Phosphorylation of DARPP-32 Inhibits Breast Cancer Cell Migration in a CREB-dependent Manner J. Biol. Chem., October 2, 2009; 284(40): 27533 - 27543. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-Z. Wang, Y.-C. Yeh, and M.-J. Tang DDR1/E-cadherin complex regulates the activation of DDR1 and cell spreading Am J Physiol Cell Physiol, August 1, 2009; 297(2): C419 - C429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. He, W. Xiong, X. Yu, R. Espinoza-Lewis, C. Liu, S. Gu, M. Nishita, K. Suzuki, G. Yamada, Y. Minami, et al. Wnt5a regulates directional cell migration and cell proliferation via Ror2-mediated noncanonical pathway in mammalian palate development Development, December 1, 2008; 135(23): 3871 - 3879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Safholm, J. Tuomela, J. Rosenkvist, J. Dejmek, P. Harkonen, and T. Andersson The Wnt-5a-Derived Hexapeptide Foxy-5 Inhibits Breast Cancer Metastasis In vivo by Targeting Cell Motility Clin. Cancer Res., October 15, 2008; 14(20): 6556 - 6563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. V. Ingman and S. A. Robertson Mammary Gland Development in Transforming Growth Factor Beta1 Null Mutant Mice: Systemic and Epithelial Effects Biol Reprod, October 1, 2008; 79(4): 711 - 717. [Abstract] [Full Text] [PDF]
|
|
