Pinski Jacek, Wang Qingcai, Quek Marcus L, Cole Ariana, Cooc Janine, Danenberg Kathleen, Danenberg Peter V
Division of Medical Oncology, University of Southern California Keck School of Medicine, USC/Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
Prostate. 2006 Aug 1;66(11):1136-43. doi: 10.1002/pros.20440.
Neuroendocrine (NE) cells are present in normal prostate and their number appears to be increased in advanced prostate cancer (PCA). In this study, we studied the effect of the phytoestrogen, genistein, on NE differentiation of LNCaP cells in vitro.
Neuroendocrine marker expression of LNCaP cells exposed to genistein was measured by immunohistochemistry, Western blot, and real-time PCR methods. Western blot analysis was used to study cell cycle and signaling pathways induced by genistein treatment.
Six days after continuous genistein treatment, the majority of genistein-surviving cancer cells underwent transdifferentiation into a NE-like phenotype overexpressing the NE markers chromogranin A, synaptophysin, serotonin, and beta-III tubulin. This NE differentiation process was associated with upregulation of the cell cycle modulators p21, p27, and p53, and activation of the MAPK and STAT3 pathways.
Our data indicate that genistein evokes not only apoptosis but also NE transdifferentiation of PCA cells.
神经内分泌（NE）细胞存在于正常前列腺组织中，在晚期前列腺癌（PCA）中其数量似乎会增加。在本研究中，我们研究了植物雌激素染料木黄酮对LNCaP细胞体外神经内分泌分化的影响。
通过免疫组织化学、蛋白质印迹法和实时PCR方法检测暴露于染料木黄酮的LNCaP细胞的神经内分泌标志物表达。蛋白质印迹分析用于研究染料木黄酮处理诱导的细胞周期和信号通路。
连续用染料木黄酮处理六天后，大多数存活的癌细胞转分化为表达神经内分泌标志物嗜铬粒蛋白A、突触素、5-羟色胺和β-III微管蛋白的神经内分泌样表型。这种神经内分泌分化过程与细胞周期调节因子p21、p27和p53的上调以及丝裂原活化蛋白激酶（MAPK）和信号转导子和转录激活子3（STAT3）信号通路的激活有关。
我们的数据表明，染料木黄酮不仅能诱导前列腺癌细胞凋亡，还能使其发生神经内分泌转分化。
