美国塔夫茨大学医学院的研究人员通过对老鼠研究发现两种与乳腺细胞分化有关的前体细胞中,其中一种或许是导致管腔型的乳腺癌的前体细胞。这项研究发表在1月19日的Cancer Cell杂志上,或将对治疗乳腺癌提供一种新的治疗靶标。
乳腺癌一般分为两类:一类是管腔型(Luminal-like)乳腺癌,这种乳腺癌对激素十分敏感,生长缓慢,是乳腺癌中最常见的一种;另一种是具有侵润性的基底细胞样型(Basal-like)乳腺癌,这种乳腺癌对激素不敏感,一般预后较差。之前有研究人员认为这两种癌症可能是由不同的前提细胞分化而来。
最近,塔夫茨大学Charlotte Kuperwasser主持的课题组对老鼠研究,发现了不同类型的乳腺前体细胞,而管腔型乳腺癌细胞来自于小叶前体细胞(lobule progenitors)的分化。研究人员还发现,这类前体细胞与一种参与细胞自我更新和分化的蛋白质cyclin D1的活性有关。研究人员使模式老鼠中cyclin D1蛋白失活,与对照组小鼠相比,cyclin D1蛋白失活组老鼠小叶祖细胞的数量很少,且不出现管腔型乳腺肿瘤。
研究人员解释,导管样祖细胞缺失cyclin D1蛋白,阻碍细胞的自我更新并中断了正常的乳腺分化,从而阻断管腔型乳腺肿瘤的形成。如果能够找到一种抑制cyclin D1蛋白活性的抑制剂,该蛋白或将成为治疗乳腺癌的新靶标。(生物谷Bioon.com)
Cell:不同乳腺癌干细胞分子特征对肿瘤发展趋势的影响
Breast Cancer:维生素D和钙能够降低女性乳腺癌风险
JCI:发现乳腺癌干细胞新表面受体
Nature:乳腺癌中的染色体重排情况
JCS:基因如何影响乳腺癌转移
Cancer Research:发现乳腺癌致病基因
生物谷推荐原始出处:
Cancer Cell, Volume 17, Issue 1, 65-76, 19 January 2010 DOI:10.1016/j.ccr.2009.11.024
Cyclin D1 Kinase Activity Is Required for the Self-Renewal of Mammary Stem and Progenitor Cells that Are Targets of MMTV-ErbB2 Tumorigenesis
Rinath Jeselsohn, Nelson E. Brown, Lisa Arendt, Ina Klebba, Miaofen G. Hu, Charlotte Kuperwasser, Philip W. Hinds
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.