| First Author | van Weele LJ | Year | 2021 |
| Journal | Stem Cell Reports | Volume | 16 |
| Issue | 2 | Pages | 228-236 |
| PubMed ID | 33482103 | Mgi Jnum | J:348887 |
| Mgi Id | MGI:6805055 | Doi | 10.1016/j.stemcr.2020.12.012 |
| Citation | van Weele LJ, et al. (2021) Depletion of Trp53 and Cdkn2a Does Not Promote Self-Renewal in the Mammary Gland but Amplifies Proliferation Induced by TNF-alpha. Stem Cell Reports 16(2):228-236 |
| abstractText | 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-alpha, Trp53(-/-)Cdkn2a(-/-) mammary basal cells exhibit amplified proliferation. |
