Accession Number:

ADA537890

Title:

Elucidating the Tumor Suppressive Role of SLITs in Maintaining the Basal Cell Niche

Descriptive Note:

Annual rept. 1 Jul 2009-30 Jun 2010

Corporate Author:

CALIFORNIA UNIV SANTA CRUZ

Personal Author(s):

Report Date:

2010-07-01

Pagination or Media Count:

16.0

Abstract:

The research performed over the last twelve months is based on the hypothesis that SLITROBO1 signaling regulates interactions between myoepithelial and luminal epithelial cells, and that loss of this activity results in the destabilization of the basal cell niche. Over the past 12 months, we have extended our analysis on the excess population of stem and progenitor cells discovered in Slit2--Slit3-- and Robo1-- mammary glands. We show that SLITROBO1 signaling restrains the proliferation of basal cells, including stem cells, and that loss of this signaling leads to increased transcription of TCFLEF targets such as Cyclin-D1. We find that SLITROBO1 signaling regulates the small GTPase Rac, possibly through the Abl tyrosine kinase, and that this regulation may link SLITROBO1 to beta-catenin. Our research promises to provide insight into the mechanisms by which normal stemprogenitor cells are regulated, leading to potential insights into how they may be deregulated upon cancerous transformation.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE