Role of Cell Senescence in Breast Cancer
Abstract
Cancer incidence rises exponentially with age. This project tested the hypothesis that cellular senescence of stromal fibroblasts contributes to the age-dependent increase in breast cancer by creating a more permissive environment for the expression of malignant phenotypes by breast epithelial cells. Here, we report that senescent human fibroblasts stimulate premalignant and malignant, but not normal, breast epithelial cells to proliferate in culture and form tumors in mice. In culture, the growth stimulation was evident when senescent cells comprised only 10% of the fibroblast population, and was equally robust whether senescence was induced by replicative exhaustion, oncogenic RAS, p14ARF or hydrogen peroxide. Moreover, it was due at least in part to soluble and insoluble factors secreted by senescent cells. In mice, senescent, much more than presenescent, fibroblasts caused premalignant and malignant epithelial cells to form tumors. Taken together, these results support our hypothesis that cellular senescence of stromal fibroblasts may contribute to breast tumorigenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA400490
Entities
People
- Ana Krtolica
Organizations
- University of California, Berkeley