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| Item Type: | Review |
|---|---|
| Title: | Reconstitution of mammary gland development in vitro: Requirement of c-met and c-erbB2 signaling for branching and alveolar morphogenesis |
| Creators Name: | Niemann, C., Brinkmann, V., Spitzer, E., Hartmann, G., Sachs, M., Naundorf, H. and Birchmeier, W. |
| Abstract: | 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. |
| Keywords: | Development of Mammary Gland, Hepatocyte Growth Factor, Neuregulin, PI3 Kinase, MAPK Kinase, Animals, Mice |
| Source: | Journal of Cell Biology |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Volume: | 143 |
| Number: | 2 |
| Page Range: | 533-545 |
| Date: | 19 October 1998 |
| Additional Information: | Copyright (c) 1998 by The Rockefeller University Press |
| Official Publication: | http://jcb.rupress.org/cgi/content/abstract/143/2/533 |
| PubMed: | View item in PubMed |
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