Search

The mammary epithelium undergoes several rounds of extensive proliferation during the female reproductive cycle. Its expansion is a tightly regulated process, fueled by the mammary stem cells and these cells' unique property of self-renewal. Sufficient new cells have to be produced to maintain the integrity of a tissue, but excessive proliferation resulting in tumorigenesis needs to be prevented. Three well-known tumor suppressors, p53, p16 I NK 4a , and p19 A RF , have been connected to the limiting of stem cell self-renewal and proliferation. Here we investigate the roles of these three proteins in the regulation of self-renewal and proliferation of mammary epithelial cells. Using mammary epithelial-specific mouse models targeting Trp53 and Cdkn2a, the gene coding for p16 INK4a and p19 ARF , we demonstrate that p53, p16 I NK 4a , and p19 A RF do not play a significant role in the limitation of normal mammary epithelium self-renewal and proliferation, whereas in the presence of the inflammatory cytokine TNF-α, Trp53 -/- Cdkn2a -/- mammary basal cells exhibit amplified proliferation., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)