Elevation of cyclic adenosine 3',5'-monophosphate potentiates activation of mitogen-activated protein kinase by growth factors in LNCaP prostate cancer cells.
Elevation of cyclic adenosine 3',5'-monophosphate potentiates activation of mitogen-activated protein kinase by growth factors in LNCaP prostate cancer cells.
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发表时间：
1999
期刊：
影响因子：
11.2
通讯作者：
Taosheng Chen;Richard W. Cho;P. Stork;M. J. Weber
中科院分区：
文献类型：
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作者：
Taosheng Chen;Richard W. Cho;P. Stork;M. J. Weber
前列腺细胞同时暴露于各种肽生长因子和神经肽，提高cAMP。生长因子和cAMP对许多细胞类型的生长、分化和运动都有很大的影响。由于丝裂原活化蛋白激酶（MAPK）是这些作用的核心，我们分析了这些激动剂在前列腺癌细胞中调节MAPK的相互作用方式。我们发现，在LNCaP前列腺癌细胞中，细胞内cAMP的升高可以增强表皮生长因子（EGF），白细胞介素6和血清激活MAPK的能力，这种增强依赖于蛋白激酶A和Rap 1。对cAMP的反应在雄激素非依赖性前列腺癌细胞系PC-3中是不同的，其中cAMP的升高轻微抑制EGF对MAPK的激活。我们还表明，用钙离子载体A23187或佛波酯佛波12-肉豆蔻酸酯13-乙酸酯处理LNCaP可激活MAPK，但这些激动剂对MAPK的激活被抑制，而不是通过增加cAMP而增强。最后，我们发现佛波醇12-肉豆蔻酸酯13-乙酸酯和白细胞介素6可以增强EGF的信号传导活性。我们的结论是，神经内分泌因子，提高cAMP敏感LNCaP前列腺癌细胞的信号肽生长因子和低水平的混合物的生长因子可以激活细胞内信号传导到更大的程度比将预测从个别激动剂的活性。
Prostate cells are simultaneously exposed to a variety of peptide growth factors and neuropeptides that elevate cAMP. Both the growth factors and cAMP have large effects on the growth, differentiation, and movement of many cell types. Because mitogen-activated protein kinase (MAPK) is central to these effects, we analyzed the ways in which these agonists interact in regulating MAPK in prostate cancer cells. We show that, in LNCaP prostate cancer cells, elevation of intracellular cAMP can potentiate the ability of epidermal growth factor (EGF), interleukin 6, and serum to activate MAPK and that this potentiation depends on protein kinase A and Rap1. The response to cAMP is different in the androgen-independent prostate cancer cell line PC-3, where elevation of cAMP slightly inhibits MAPK activation by EGF. We also show that treatment of LNCaP with the calcium ionophore A23187 or the phorbol ester phorbol 12-myristate 13-acetate activates MAPK, but the activation of MAPK by these agonists is inhibited rather than potentiated by increasing cAMP. Finally, we show that phorbol 12-myristate 13-acetate and interleukin 6 can potentiate the signaling activity of EGF. We conclude that neuroendocrine factors that elevate cAMP sensitize LNCaP prostate cancer cells to signaling by peptide growth factors and that low levels of mixtures of growth factors can activate intracellular signaling to a greater degree than would be predicted from the activity of the individual agonists.