QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online June 25, 2007
doi: 10.1242/10.1242/jcs.03467

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fischer, A. Articles by Theuring, F. Search for Related Content PubMed PubMed Citation Articles by Fischer, A. Articles by Theuring, F. Social Bookmarking                         What's this?

Impaired tight junction sealing and precocious involution in mammary glands of PKN1 transgenic mice

Andreas Fischer¹, Heiko Stuckas¹, Markus Gluth¹, Tanya D. Russell², Michael C. Rudolph², Neal E. Beeman², Sebastian Bachmann³, Shinobu Umemura⁴, Yasuhiro Ohashi^5,, Margaret C. Neville^2,*, and Franz Theuring^1,*,

¹ Institute of Pharmacology, Center for Cardiovascular Research, Charité University Medicine, 10115 Berlin, Germany
² Department of Physiology and Biophysics, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
³ Department of Anatomy, Center for Cardiovascular Research, Charité University Medicine, Berlin, Germany
⁴ Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa, Japan
⁵ Laboratory of Molecular Biology, Nihon Schering K.K., Osaka 532-0004, Japan

Authors for correspondence (e-mail: Peggy.Neville{at}uchsc.edu; Franz.Theuring{at}charite.de)

Accepted 26 April 2007

The mammary gland undergoes a complex set of changes to establish copious milk secretion at parturition. To test the hypothesis that signaling through the Rho pathway plays a role in secretory activation, transgenic mice expressing a constitutively activated form of the Rho effector protein PKN1 in the mammary epithelium were generated. PKN1 activation had no effect in late pregnancy but inhibited milk secretion after parturition, diminishing the ability of transgenic dams to support a litter. Mammary gland morphology as well as increased apoptosis and expression of IFGBP5 and TGFβ3 suggest precocious involution in these animals. Furthermore, tight junction sealing at parturition was impaired in transgenic mammary glands as demonstrated by intraductal injection of [¹⁴C]sucrose. Consistent with this finding, tight junction sealing in response to glucocorticoid stimulation was highly impaired in EpH4 mammary epithelial cells expressing constitutively activated PKN1, whereas expression of a dominant-negative PKN1 mutant resulted in accelerated tight junction sealing in vitro. Tight junction formation was not impaired as demonstrated by the correct localization of occludin and ZO1 at the apical cell borders. Our results provide evidence that PKN1 participates in the regulation of tight junction sealing in the mammary gland by interfering with glucocorticoid signaling.

Key words: PKN1, Tight junction sealing, Mammary gland development, Secretory activation

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in JCS:

Rho signalling delivers the milk

JCS 2007 120: 1302. [Full Text]  

This article has been cited by other articles:

				F. Carrozzino, P. Pugnale, E. Feraille, and R. Montesano Inhibition of basal p38 or JNK activity enhances epithelial barrier function through differential modulation of claudin expression Am J Physiol Cell Physiol, January 1, 2009; 297(3): C775 - C787. [Abstract] [Full Text] [PDF]