Long term increased expression of the short form 1b prolactin receptor in PC-3 human prostate cancer cells decreases cell growth and migration, and causes multiple changes in gene expression consistent with reduced invasive capacity.
Long term increased expression of the short form 1b prolactin receptor in PC-3 human prostate cancer cells decreases cell growth and migration, and causes multiple changes in gene expression consistent with reduced invasive capacity.
复制标题
DOI：
10.1002/pros.21036
复制
发表时间：
2010-01-01
期刊：
影响因子：
2.8
通讯作者：
Walker, Ameae M.
中科院分区：
文献类型：
--
作者：
Huang, Kuang-tzu;Walker, Ameae M.
关键词：
我们已经证明，用选择性催乳素(PRL)受体调节剂S179D PRL处理人前列腺癌细胞，在体外抑制生长，在体内抑制异种移植瘤的启动和生长。S179D PRL治疗还上调了短形式1b(SF1b)PRL受体的表达，该受体的激活上调了细胞周期调节蛋白p21的表达。我们通过建立PC-3衍生的稳定细胞系来研究长期增加SF1b表达和激活的后果，其水平与S179D PRL治疗的结果相当。PC-3衍生的稳定细胞系表达一种成分活性形式的SF1b，即ΔS2 SF1b。Δ-S2、SF1b表达增加，细胞生长和迁移减少。这伴随着细胞-基质相互作用的增加，当细胞被接种在基底膜组件上时，细胞-细胞聚集。实时荧光定量聚合酶链式反应检测侵袭能力相关基因的表达。尤其值得注意的是，尿激酶型纤溶酶原激活物及其受体uPAR的蛋白表达减少，其抑制物PAI-1和2的表达增加。在ΔS2 SF1b表达增加的细胞中，碱性成纤维细胞生长因子和血管内皮生长因子的表达也减少。我们的结论是，至少部分S179D PRL的有益作用是SF1b表达增加的结果，并且从长期来看，SF1b表达和激活的增加继续具有潜在的好处。
We have shown that treatment of human prostate cancer cells with the selective prolactin (PRL) receptor modulator, S179D PRL, inhibits growth in vitro, and the initiation and growth of xenografts in vivo. S179D PRL treatment also upregulates expression of the short form 1b (SF1b) PRL receptor, activation of which upregulates expression of the cell cycle-regulating protein, p21. We examined the consequences of long term increased expression and activation of SF1b, at levels comparable to those resulting from treatment with S179D PRL, by creating PC-3-derived stable cell lines expressing a constitutively-active form of SF1b, ΔS2 SF1b. Increased expression of ΔS2 SF1b decreased growth and migration of the cells. This was accompanied by an increase in cell-matrix interactions, and cell-cell aggregation when cells were plated on basement membrane components. Real-time PCR evaluated the expression of genes related to invasive capacity. Of particular interest was decreased expression of the protease, urokinase-type plaminogen activator, and its receptor, uPAR, and increased expression of its inhibitors, PAI-1 and 2. Also decreased in cells with increased expression of ΔS2 SF1b was expression of basic fibroblast growth factor and vascular endothelial growth factor. We conclude that at least part of the beneficial effects of S179D PRL is the result of increased expression of SF1b, and that the effects of increased expression and activation of SF1b continue to be of potential benefit in the long term.
登录
查看更多内容
影响因子：
15.9
作者：
Conacci-Sorrell, M;Zhurinsky, J;Ben-Ze'ev, A
通讯作者：
Ben-Ze'ev, A
影响因子：
56.9
作者：
He, TC;Sparks, AB;Kinzler, KW
通讯作者：
Kinzler, KW
影响因子：
4.8
作者：
Kindblom, J;Dillner, K;Wennbo, H
通讯作者：
Wennbo, H
影响因子：
3.4
作者：
Forbes, K;Gillette, K;Sehgal, I
通讯作者：
Sehgal, I
影响因子：
4.8
作者：
Chen, TJ;Kuo, CB;Walker, AM
通讯作者：
Walker, AM