Role of Cell Senescence in Breast Cancer
Abstract
Cancer incidence rises exponentially with age. This project tests the hypothesis that replicative 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 both mouse and human immortal pre-malignant breast epithelial cell lines show increased proliferation in the presence of senescent, compared to presenescent, human fibroblasts. At least part of this senescent fibroblast-derived mitotic activity is due to secreted insoluble matrix components. The effect of senescent fibroblasts on breast epithelial cell proliferation is observable even when they are present as only 10% of a mixed population of presenescent and senescent fibroblasts. One very important implication of this finding is that the accumulation of even a few senescent cells in the aging organism may stimulate unconstrained epithelial growth and thus contribute to malignant transformation of the surrounding breast epithelium. Taken together these results support our hypothesis that replicative senescence of stromal fibroblasts may contribute to the development of malignant properties of breast epithelial cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA384125
Entities
People
- Ana Krtolica
- J. Capisi
Organizations
- University of California, Berkeley