美國塔夫茨大學醫學院的研究人員通過對老鼠研究發現兩種與乳腺細胞分化有關的前體細胞中,其中一種或許是導致管腔型的乳腺癌的前體細胞。這項研究發表在1月19日的Cancer Cell雜誌上,或將對治療乳腺癌提供一種新的治療靶標。
乳腺癌一般分為兩類:一類是管腔型(Luminal-like)乳腺癌,這種乳腺癌對激素十分敏感,生長緩慢,是乳腺癌中最常見的一種;另一種是具有侵潤性的基底細胞樣型(Basal-like)乳腺癌,這種乳腺癌對激素不敏感,一般預後較差。之前有研究人員認為這兩種癌症可能是由不同的前提細胞分化而來。
最近,塔夫茨大學Charlotte Kuperwasser主持的課題組對老鼠研究,發現了不同類型的乳腺前體細胞,而管腔型乳腺癌細胞來自於小葉前體細胞(lobule progenitors)的分化。研究人員還發現,這類前體細胞與一種參與細胞自我更新和分化的蛋白質cyclin D1的活性有關。研究人員使模式老鼠中cyclin D1蛋白失活,與對照組小鼠相比,cyclin D1蛋白失活組老鼠小葉祖細胞的數量很少,且不出現管腔型乳腺腫瘤。
研究人員解釋,導管樣祖細胞缺失cyclin D1蛋白,阻礙細胞的自我更新並中斷了正常的乳腺分化,從而阻斷管腔型乳腺腫瘤的形成。如果能夠找到一種抑制cyclin D1蛋白活性的抑制劑,該蛋白或將成為治療乳腺癌的新靶標。(生物谷Bioon.com)
Cell:不同乳腺癌幹細胞分子特徵對腫瘤發展趨勢的影響
Breast Cancer:維生素D和鈣能夠降低女性乳腺癌風險
JCI:發現乳腺癌幹細胞新表面受體
Nature:乳腺癌中的染色體重排情況
JCS:基因如何影響乳腺癌轉移
Cancer Research:發現乳腺癌致病基因
生物谷推薦原始出處:
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.