Int-3 Oncogene in Normal and Neoplastic Breast Development.
Abstract
Elongation and branching of epithelial ducts is required for mammary gland development. Branching morphogenesis of mammary TAC-2 cells was used to examine Wnts, HGF, TGF-beta and Notch receptors in branching morphogenesis. Wnt-1 induced the elongation and branching of epithelial tubules, and strongly cooperated with either HGF or TGF-beta2 in this activity. The Notch4(int-3) mammary oncoprotein, inhibited the branching morphogenesis induced by HGF and TGF-beta2. The minimal domain of Notch4(int-3) required consists of the CBF-1 interaction domain and the cdc 10 repeats. Co-expression of Wnt-1 and Notch4(int-3) demonstrates that Wnt-1 overrides the Notch-mediated inhibition of ductal morphogenesis. These data suggest that Wnt and Notch signaling play opposite roles in mammary gland development. We describe genetic evidence indicating that sel-10 is a negative regulator of lin-12/Notch mediated signaling in C. elegans. Sequence analysis shows that SEL-10 is a member of the CDC4 family of proteins with a potential human ortholog. Co-immunoprecipitation data indicate that C. elegans SEL-10 complexes with LIN-12 and with murine Notch4. We propose that SEL-10 promotes the ubiquitin-mediated turnover of LIN-12/Notch proteins.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1997
- Accession Number
- ADA336683
Entities
People
- Jan K. Kitajewski
Organizations
- Columbia University