Accession Number:

ADA456007

Title:

Notch and VEGF Interactions in Breast Cancer

Descriptive Note:

Final rept. 1 Apr 2003-31 Mar 2006

Corporate Author:

COLUMBIA UNIV NEW YORK

Personal Author(s):

Report Date:

2006-04-01

Pagination or Media Count:

19.0

Abstract:

The proposal objective is to define Notch and VEGFR-3 in breast cancer. We investigated this relationship in primary endothelial cell cultures, mouse embryos, human breast tumors, and mouse mammary tumor xenografts. We demonstrate that Notch signaling promotes VEGFR-3 messages and protein in both primary endothelial cell cultures and mouse embryos in which Notch4 signaling is activated within the endothelium. In normal breast tissue, Notch1, Notch4 and Dll4 are expressed in the ductal epithelium and vasculature, whereas Jagged1 is restricted to the vasculature. Moreover, Notch is actively signaling within a subset of normal ductal epithelial cells. In malignant mammary tissue, Notch1, Notch4, Dll4, and VEGFR-3 were expressed in both epithelial and endothelia cells. Though, there were differences in the patterns of expression that suggest Notch1 and Notch4 have different functions in tumor angiogenesis. We also show for the first time that Notch1 and Notch4 are expressed in breast tumor lymphatic endothelial cells and most likely actively signaling. We have developed a Notch1 antagonist that blocks ligand dependent Notch signaling using in vitro coculture assays. We found that this Notch1 antagonist inhibits mouse mammary tumor growth in a xenograft mouse model.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE