Aging, Breast Cancer and the Mouse Model
Abstract
Mammalian cells can respond to stress or damage by undergoing a permanent cell cycle arrest termed cellular senescence. The senescence response suppresses the development of cancer, but the altered cellular functions that accompany this response may contribute to aging. Our study addressed whether and how mouse senescent stroma contributes to breast cancer and what role senescent mouse fibroblasts have in this process. We established for the first time an adequate and reliable in vitro mouse model mimicking human senescence, with extensive similarities. 3% oxygen culture condition combined with X-irradiation is the prerequisite to imitate human fibroblast senescence. Under these conditions, human and mouse senescent stromal cells disrupt normal mammary epithelial differentiation, and promote hyper- proliferation of pre-neoplastic mammary epithelial cells. Our findings suggest that senescent fibroblasts can disrupt the stromal-epithelial interactions, ultimately promoting breast cancer with age. By establishing such a mouse model, we hope to improve the scientific possibilities exploring the effect of aging on breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2005
- Accession Number
- ADA444743
Entities
People
- Jean-philippe Coppe
Organizations
- University of California, Berkeley