JCB logo
Accuri Cytometers
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 1798K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Niemann, C.
Right arrow Articles by Birchmeier, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Niemann, C.
Right arrow Articles by Birchmeier, W.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

© The Rockefeller University Press, 0021-9525/1998//533 $5.00
The Journal of Cell Biology, Volume 143, Number 2, , 1998 533-545

Regular Articles

Reconstitution of Mammary Gland Development In Vitro: Requirement of c-met and c-erbB2 Signaling for Branching and Alveolar Morphogenesis



Catherin Niemann, Volker Brinkmann, Eva Spitzer, Guido Hartmann, Martin Sachs, Helga Naundorf, and Walter Birchmeier

Max-Delbrück-Center for Molecular Medicine, D-13122 Berlin, Germany

We have established a cell culture system that reproduces morphogenic processes in the developing mammary gland. EpH4 mouse mammary epithelial cells cultured in matrigel form branched tubules in the presence of hepatocyte growth factor/scatter factor (HGF/SF), the ligand of the c-met tyrosine kinase receptor. In contrast, alveolar structures are formed in the presence of neuregulin, a ligand of c-erbB tyrosine kinase receptors. These distinct morphogenic responses can also be observed with selected human mammary carcinoma tissue in explant culture. HGF/SF-induced branching was abrogated by the PI3 kinase inhibitors wortmannin and LY294002. In contrast, neuregulin- induced alveolar morphogenesis was inhibited by the MAPK kinase inhibitor PD98059. The c-met–mediated response could also be evoked by transfection of a c-met specific substrate, Gab1, which can activate the PI3 kinase pathway. An activated hybrid receptor that contained the intracellular domain of c-erbB2 receptor suffices to induce alveolar morphogenesis, and was observed in the presence of tyrosine residues Y1028, Y1144, Y1201, and Y1226/27 in the substrate-binding domain of c-erbB2. Our data demonstrate that c-met and c-erbB2 signaling elicit distinct morphogenic programs in mammary epithelial cells: formation of branched tubules relies on a pathway involving PI3 kinase, whereas alveolar morphogenesis requires MAPK kinase.

Key Words: development of mammary gland • hepatocyte growth factor • neuregulin • PI3 kinase • MAPK kinase

Abbreviations used in this paper: EGF, epidermal growth factor; HGF/ SF, hepatocyte growth factor/scatter factor; KGF, keratinocyte growth factor; NGF, nerve growth factor.

Address all correspondence to W. Birchmeier, Max-Delbrück-Center for Molecular Medicine, Robert-Rossle-Strasse 10, D-13122 Berlin, Germany. Tel.: (49) 30-9406-3800. Fax: (49) 30-9406-2656. E-mail: wbirch{at}mdc-berlin.de

V. Brinkmann's present address is Max-Planck-Institute for Infection Biology, Monbijoustrasse 2, 10117 Berlin, Germany.

E. Spitzer's present address is Institute for Medicine of Molecular Diagnostic, Frankfurter Allee 65, 10247 Berlin, Germany.

G. Hartmann's present address is Glaxo Wellcome Research and Development, Gunnelswood Road, Stevenage SG1 2NY, UK.


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


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents