Adult murine prostate basal and luminal cells are self-sustained lineages that can both serve as targets for prostate cancer initiation.
Adult murine prostate basal and luminal cells are self-sustained lineages that can both serve as targets for prostate cancer initiation.
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DOI：
10.1016/j.ccr.2012.01.005
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发表时间：
2012-02-14
期刊：
影响因子：
50.3
通讯作者：
Xin L
中科院分区：
文献类型：
--
作者：
Choi N;Zhang B;Zhang L;Ittmann M;Xin L
前列腺上皮谱系等级和前列腺癌的细胞起源仍然没有充分的定义。使用谱系追踪方法，我们表明成年啮齿动物前列腺基底细胞和腔细胞在体内独立自我维持。破坏任一谱系中的肿瘤抑制因子Pten可导致前列腺癌的发生。然而，所产生的肿瘤的细胞组成和发病动力学是独特的。前列腺腔细胞对Pten零诱导的有丝分裂信号更敏感。相反，基底细胞对直接转化有抵抗力。相反，Pten活性的丧失会诱导基底细胞分化为具有转化能力的管腔细胞。我们的研究表明，上皮分化的失调是基底细胞起源的前列腺癌起始的关键步骤。
The prostate epithelial lineage hierarchy and the cellular origin for prostate cancer remain inadequately defined. Using a lineage tracing approach, we show that adult rodent prostate basal and luminal cells are independently self-sustained in vivo. Disrupting the tumor suppressor Pten in either lineage led to prostate cancer initiation. However, the cellular composition and onset dynamics of the resulting tumors are distinctive. Prostate luminal cells are more responsive to Pten null-induced mitogenic signaling. In contrast, basal cells are resistant to direct transformation. Instead, loss of Pten activity induces the capability of basal cells to differentiate into transformation-competent luminal cells. Our study suggests that deregulation of epithelial differentiation is a critical step for the initiation of prostate cancers of basal cell origin.
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DOI：
10.1126/science.1189992
发表时间：
2010-07-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Goldstein AS;Huang J;Guo C;Garraway IP;Witte ON
通讯作者：
Witte ON
影响因子：
--
作者：
Liu, June;Pascal, Laura E.;Wang, Zhou
通讯作者：
Wang, Zhou
影响因子：
6
作者：
Park, JH;Walls, JE;Cardiff, RD
通讯作者：
Cardiff, RD
影响因子：
11.2
作者：
Jaamaa, Sari;af Hallstrom, Taija M.;Laiho, Marikki
通讯作者：
Laiho, Marikki
影响因子：
2.6
作者：
Iczkowski, Kenneth A;Lucia, M Scott
通讯作者：
Lucia, M Scott