Accession Number : ADA337513

Title :   Role of the Int-3 Oncogene in Mammary Gland Development and Tumorigenesis.

Descriptive Note : Annual rept. 15 Aug 96-14 Aug 97

Corporate Author : COLUMBIA UNIV NEW YORK

Personal Author(s) : Kitajewski, Jan ; Uyttendaele, Hendrik

PDF Url : ADA337513

Report Date : SEP 1997

Pagination or Media Count : 71

Abstract : Elongation and branching of epithelial ducts is a crucial event during the development of the mammary gland. Branching morphogenesis of the mouse mammary epithelial TAC-2 cell line was used as an assay to examine the role of Wnts, HGF, TGF-% and the Notch receptors in branching morphogenesis. Wnt-l was found to induce the elongation and branching of epithelial tubules, like HUF and TGF-%2, and to strongly cooperate with either HGF or TGF-%2 in this activity. The Notch4(int-3) mammary oncoprotein, an activated form of the Notch4 receptor, inhibited the branching morphogenesis normally induced by HOF and TGF-%. The minimal domain within the Notch4(int-3) protein required to inhibit morphogenesis consists of the CBF-1 interaction domain and the cdc 10 repeat domain. Co-expression of Wnt- 1 and Notch4(int-3) demonstrates that Wnt- 1 can overcome the Notch-mediated inhibition of ductal morphogenesis. These data suggest that Wnt and Notch signaling may play opposite roles in mammary gland development, a finding consistent with the convergence of the wingless and Notch signaling pathways found in Drosophila.

Descriptors :   *CELLS(BIOLOGY), *MAMMARY GLANDS, *ONCOGENIC VIRUSES, EPITHELIUM, SIGNALS, DUCTS, ELONGATION, MORPHOGENESIS, DROSOPHILA.

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE