Reactivation of embryonic nodal signaling is associated with tumor progression and promotes the growth of prostate cancer cells.
Reactivation of embryonic nodal signaling is associated with tumor progression and promotes the growth of prostate cancer cells.
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DOI：
10.1002/pros.21335
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发表时间：
2011-08-01
期刊：
影响因子：
2.8
通讯作者：
Hendrix, Mary J. C.
中科院分区：
文献类型：
--
作者：
Lawrence, Mitchell G.;Margaryan, Naira V.;Loessner, Daniela;Collins, Angus;Kerr, Kris M.;Turner, Megan;Seftor, Elisabeth A.;Stephens, Carson R.;Lai, John;Postovit, Lynne-Marie;Clements, Judith A.;Hendrix, Mary J. C.
Nodal是转化生长因子β（TGFβ）超家族的成员，其指导胚胎图案形成并促进肿瘤细胞的可塑性和致瘤性，但其在前列腺中的作用尚不清楚。本研究的目的是表征Nodal在前列腺癌中的表达和功能，并确定其是否与其他TGFβ配体一样调节雄激素受体（AR）活性。使用组织微阵列的免疫组织化学和前列腺细胞系的蛋白质印迹研究结表达。使用Matrigel和软琼脂生长测定法检查Nodal的功能作用。Nodal和AR信号传导之间的串扰用荧光素酶报告基因测定和内源性雄激素调节基因的表达进行评估。与良性前列腺标本相比，在癌症中观察到Nodal表达显着增加。Nodal仅在DU 145和PC 3细胞中表达。所有细胞系都表达Nodal的共同受体Cripto-1，但缺乏Lefty，这是Nodal信号传导的关键负调节因子。重组人Nodal在DU 145和LNCaP细胞中触发下游Smad 2磷酸化，并且稳定转染pre-pro-Nodal增强了LNCaP细胞在Matrigel和软琼脂中的生长。最后，Nodal减弱了AR信号传导，降低了荧光素酶测定中PSA启动子构建体的活性，并下调了雄激素调节基因的内源性表达。异常的Nodal信号通路在前列腺癌细胞中重新表达并具有功能活性。
Nodal is a member of the Transforming Growth Factor β (TGFβ) superfamily that directs embryonic patterning and promotes the plasticity and tumorigenicity of tumor cells, but its role in the prostate is unknown. The goal of this study was to characterize the expression and function of Nodal in prostate cancer and determine whether, like other TGFβ ligands, it modulates androgen receptor (AR) activity. Nodal expression was investigated using immunohistochemistry of tissue microarrays and Western blots of prostate cell lines. The functional role of Nodal was examined using Matrigel and soft agar growth assays. Cross-talk between Nodal and AR signaling was assessed with luciferase reporter assays and expression of endogenous androgen regulated genes. Significantly increased Nodal expression was observed in cancer compared with benign prostate specimens. Nodal was only expressed by DU145 and PC3 cells. All cell lines expressed Nodal’s co-receptor, Cripto-1, but lacked Lefty, a critical negative regulator of Nodal signaling. Recombinant human Nodal triggered downstream Smad2 phosphorylation in DU145 and LNCaP cells, and stable transfection of pre-pro-Nodal enhanced the growth of LNCaP cells in Matrigel and soft agar. Finally, Nodal attenuated AR signaling, reducing the activity of a PSA promoter construct in luciferase assays and down-regulating the endogenous expression of androgen regulated genes. An aberrant Nodal signaling pathway is re-expressed and functionally active in prostate cancer cells.
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影响因子：
4.6
作者：
Mesnard, Daniel;Guzman-Ayala, Marcela;Constam, Daniel B.
通讯作者：
Constam, Daniel B.
影响因子：
4.8
作者：
Gerdes, MJ;Dang, TD;Rowley, DR
通讯作者：
Rowley, DR
影响因子：
4.8
作者：
Dhanasekaran, SM;Dash, A;Chinnaiyan, AM
通讯作者：
Chinnaiyan, AM
DOI：
10.1152/ajpendo.00443.2003
发表时间：
2004-06-01
影响因子：
5.1
作者：
Fujii, Y;Kawakami, S;Kihara, K
通讯作者：
Kihara, K
影响因子：
4.8
作者：
Kelber, Jonathan A.;Shani, Gidi;Gray, Peter C.
通讯作者：
Gray, Peter C.