Ontiveros Christopher S, Salm Sarah N, Wilson E Lynette
Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA.
Prostate. 2008 Sep 1;68(12):1263-72. doi: 10.1002/pros.20770.
We previously reported that prostatic stem/progenitor cells are concentrated in the proximal region of prostatic ducts and express stem cell antigen 1 (Sca-1). As Wnt signaling is important for the maintenance of stem cells, we determined whether Sca-1 expressing cells also express Axin2, as Axin2 expression is highly suggestive of active Wnt signaling.
Axin2 promoter reporter mice were used for whole mount and fluorescence activated cell sorting (FACS) analysis to determine its expression in the prostate. Axin2 expressing cells were also examined for the co-expression of Sca-1. We also used a chemical activator of Wnt signaling, BIO, to determine the effects of Wnt signaling on the growth of primary prostate cells in vitro.
We show that Axin2 expression is present in all lobes and is regulated by androgens with the highest Axin2 expression in the lateral and dorsal prostate. Furthermore, a fraction of Axin2 expressing cells co-express Sca-1, suggesting that some progenitor cells have active Wnt signaling. Lastly, we demonstrate that activation of the Wnt pathway may result in increased growth, consistent with a role for Wnt signaling in maintenance and/or expansion of the progenitor cell population.
Axin2 expressing cells that co-express Sca-1 are present in all prostate lobes suggesting that progenitor cells reside within the Wnt active population. An understanding of the basic biology of signaling pathways mediating growth in the prostate may lead to rational therapies to treat benign prostatic hyperplasia and prostate cancer.
我们之前报道过前列腺干/祖细胞集中在前列腺导管的近端区域并表达干细胞抗原1(Sca-1)。由于Wnt信号通路对干细胞的维持很重要,我们确定表达Sca-1的细胞是否也表达Axin2,因为Axin2的表达强烈提示Wnt信号通路处于激活状态。
使用Axin2启动子报告基因小鼠进行整体装片和荧光激活细胞分选(FACS)分析,以确定其在前列腺中的表达。还检测了表达Axin2的细胞中Sca-1的共表达情况。我们还使用Wnt信号通路的化学激活剂BIO来确定Wnt信号通路对原代前列腺细胞体外生长的影响。
我们发现Axin2在所有叶中均有表达,且受雄激素调节,在前列腺外侧叶和背叶中Axin2表达最高。此外,一部分表达Axin2的细胞共表达Sca-1,这表明一些祖细胞具有活跃的Wnt信号通路。最后,我们证明Wnt通路的激活可能导致生长增加,这与Wnt信号通路在祖细胞群体的维持和/或扩增中的作用一致。
共表达Sca-1的Axin2表达细胞存在于所有前列腺叶中,这表明祖细胞存在于Wnt活跃群体中。了解介导前列腺生长的信号通路的基本生物学特性可能会带来治疗良性前列腺增生和前列腺癌的合理疗法。