Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Science. 2010 Jul 30;329(5991):568-71. doi: 10.1126/science.1189992.
Luminal cells are believed to be the cells of origin for human prostate cancer, because the disease is characterized by luminal cell expansion and the absence of basal cells. Yet functional studies addressing the origin of human prostate cancer have not previously been reported because of a lack of relevant in vivo human models. Here we show that basal cells from primary benign human prostate tissue can initiate prostate cancer in immunodeficient mice. The cooperative effects of AKT, ERG, and androgen receptor in basal cells recapitulated the histological and molecular features of human prostate cancer, with loss of basal cells and expansion of luminal cells expressing prostate-specific antigen and alpha-methylacyl-CoA racemase. Our results demonstrate that histological characterization of cancers does not necessarily correlate with the cellular origins of the disease.
腔细胞被认为是人类前列腺癌的起源细胞，因为这种疾病的特征是腔细胞扩张和基底细胞缺失。然而，由于缺乏相关的体内人类模型，以前没有报道过针对人类前列腺癌起源的功能研究。在这里，我们表明，来自原发性良性人前列腺组织的基底细胞可以在免疫缺陷小鼠中引发前列腺癌。基底细胞中 AKT、ERG 和雄激素受体的协同作用再现了人类前列腺癌的组织学和分子特征，表现为基底细胞丢失和表达前列腺特异性抗原和α-甲基酰基辅酶 A 消旋酶的腔细胞扩张。我们的结果表明，癌症的组织学特征不一定与疾病的细胞起源相关。
