Accession Number:

ADA336683

Title:

Int-3 Oncogene in Normal and Neoplastic Breast Development.

Descriptive Note:

Annual rept. 1 Sep 96-31 Aug 97

Corporate Author:

COLUMBIA UNIV NEW YORK

Personal Author(s):

Report Date:

1997-09-01

Pagination or Media Count:

111.0

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 Notch4int-3 mammary oncoprotein, inhibited the branching morphogenesis induced by HGF and TGF-beta2. The minimal domain of Notch4int-3 required consists of the CBF-1 interaction domain and the cdc 10 repeats. Co-expression of Wnt-1 and Notch4int-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-12Notch 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-12Notch proteins.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE