Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, CA, USA.
Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, CA, USA; Department of Stem Cell Biotechnology, California State University Channel Islands, Camarillo, CA, USA.
Stem Cell Reports. 2021 Feb 9;16(2):228-236. doi: 10.1016/j.stemcr.2020.12.012. Epub 2021 Jan 21.
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, and p19, 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 and p19, we demonstrate that p53, p16, and p19 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, Trp53Cdkn2a mammary basal cells exhibit amplified proliferation.
在女性生殖周期中，乳腺上皮经历了几轮广泛的增殖。其扩张是一个受到严格调控的过程，由乳腺干细胞及其自我更新的独特特性驱动。需要产生足够的新细胞来维持组织的完整性，但需要防止过度增殖导致肿瘤发生。三个著名的肿瘤抑制因子，p53、p16 和 p19，已经与限制干细胞自我更新和增殖有关。在这里，我们研究了这三种蛋白在调节乳腺上皮细胞自我更新和增殖中的作用。使用针对 Trp53 和 Cdkn2a（编码 p16 和 p19 的基因）的乳腺上皮特异性小鼠模型，我们证明 p53、p16 和 p19 在限制正常乳腺上皮细胞自我更新和增殖方面没有起到显著作用，而在炎症细胞因子 TNF-α 的存在下，Trp53Cdkn2a 乳腺基底细胞表现出扩增的增殖。
