Basis of Persistent Microenvironment Perturbation in Irradiated Human Mammary Epithelial Cells
Abstract
Genomic instability, evidence by non-clonal chromosomal abnormalities, delayed death, and increased recombination, is increased in the progeny of irradiated cells. We have -shown that radiation exposed non-malignant human mammary epithelial cells undergo aberrant acinar morphogenesis when suspended in a basement membrane type matrix. The loss of cell-cell adhesion, down-regulation of E-cadherin and gap junctions, and perturbed integrin expression shown by irradiated cells is consistent with neoplastic progression. In the current proposal, we wish to test the hypothesis that persistent disruption of extracellular signaling in irradiated cells promotes genomic instability. We will measure centrosomes, chromosome number and aneuploidy in the daughters of irradiated cells, determine the dose dependence, and how transforming growth factor beta, which augments the morphogenic disruption, affects genomic instability. We will also test if the radiation phenotype can be transmitted to unirradiated cells and whether its prevalence in irradiated cells is epigenetic in nature. These exploratory studies will define non- mutational mechanisms by which ionizing radiation, a known carcinogen of human breast, affects carcinogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA428163
Entities
People
- Mary H. Barcellos-hoff
Organizations
- University of California, Berkeley