Promotion of variant human mammary epithelial cell outgrowth by ionizing radiation: an agent-based model supported by in vitro studies |
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Authors: | Rituparna Mukhopadhyay Sylvain V Costes Alexey V Bazarov William C Hines Mary Helen Barcellos-Hoff Paul Yaswen |
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Institution: | (1) Life Sciences Division, Lawrence Berkeley National Laboratory, 94720 Berkeley, CA, USA;(2) Department of Laboratory Medicine, University of California, 94143 San Francisco, CA, USA;(3) Department of Radiation Oncology, New York University School of Medicine, 10016 New York, NY, USA |
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Abstract: | Introduction Most human mammary epithelial cells (HMEC) cultured from histologically normal breast tissues enter a senescent state termed
stasis after 5 to 20 population doublings. These senescent cells display increased size, contain senescence associated β-galactosidase
activity, and express cyclin-dependent kinase inhibitor, p16INK4A (CDKN2A; p16). However, HMEC grown in a serum-free medium, spontaneously yield, at low frequency, variant (v) HMEC that are
capable of long-term growth and are susceptible to genomic instability. We investigated whether ionizing radiation, which
increases breast cancer risk in women, affects the rate of vHMEC outgrowth. |
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