Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
Cancer Cell. 2010 Jan 19;17(1):65-76. doi: 10.1016/j.ccr.2009.11.024.
Transplantation studies have demonstrated the existence of mammary progenitor cells with the ability to self-renew and regenerate a functional mammary gland. Although these progenitors are the likely targets for oncogenic transformation, correlating progenitor populations with certain oncogenic stimuli has been difficult. Cyclin D1 is required for lobuloalveolar development during pregnancy and lactation as well as MMTV-ErbB2- but not MMTV-Wnt1-mediated tumorigenesis. Using a kinase-deficient cyclin D1 mouse, we identified two functional mammary progenitor cell populations, one of which is the target of MMTV-ErbB2. Moreover, cyclin D1 activity is required for the self-renewal and differentiation of mammary progenitors because its abrogation leads to a failure to maintain the mammary epithelial regenerative potential and also results in defects in luminal lineage differentiation.
移植研究表明存在具有自我更新和再生功能性乳腺能力的乳腺祖细胞。尽管这些祖细胞可能是致癌转化的靶标，但将祖细胞群体与某些致癌刺激相关联一直很困难。Cyclin D1 是妊娠和哺乳期形成小叶腺泡所必需的，并且是 MMTV-ErbB2 而不是 MMTV-Wnt1 介导的肿瘤发生所必需的。使用激酶缺陷型 cyclin D1 小鼠，我们鉴定了两种功能性乳腺祖细胞群体，其中一种是 MMTV-ErbB2 的靶标。此外，cyclin D1 的活性是乳腺祖细胞自我更新和分化所必需的，因为其缺失会导致无法维持乳腺上皮的再生潜能，并且还导致管腔谱系分化缺陷。
