Overexpression of HepaCAM Inhibits Cell Viability and Motility Through Suppressing Nucleus Translocation of Androgen Receptor and ERK Signaling in Prostate Cancer
Overexpression of HepaCAM Inhibits Cell Viability and Motility Through Suppressing Nucleus Translocation of Androgen Receptor and ERK Signaling in Prostate Cancer
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DOI：
10.1002/pros.22817
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发表时间：
2014-07-01
期刊：
影响因子：
2.8
通讯作者：
Luo, Chunli
中科院分区：
文献类型：
--
作者：
Song, Xuedong;Wang, Yin;Luo, Chunli
背景资料。HepaCAM在多种人类癌症中被抑制，并参与细胞黏附、生长、迁移、侵袭和生存。方法：应用RT-PCR、Western blotting和免疫组织化学方法分别检测了前列腺癌细胞株RWPE-1、LNCaP、DU145、PC3和75例人前列腺癌组织中HepaCAM的表达。用WST-8比色法检测细胞增殖能力。通过伤口愈合和Transwell实验检测HepaCAM在前列腺癌细胞迁移和侵袭中的作用。并用流式细胞仪观察前列腺癌细胞的凋亡情况。结果在前列腺癌组织中表达明显下调，在前列腺癌细胞中未检测到表达。然而，低表达的HepaCAM与前列腺癌的临床病理特征无统计学相关性。在前列腺癌细胞中过表达的HepaCAM抑制了细胞的增殖、迁移和侵袭，诱导了细胞的凋亡。同时，HepaCAM可阻止雄激素受体从胞浆转位到胞核，并下调MAPK/ERK信号转导。结论：我们的研究结果提示，HepaCAM在前列腺癌中起到了肿瘤抑制作用。HepaCAM可能通过抑制雄激素受体的核转位，下调ERK信号通路，从而抑制细胞的存活和运动。因此，研究表明，HepaCAM可能是前列腺癌的潜在治疗靶点。(C)2014Wiley期刊公司。
BACKGROUND. HepaCAM is suppressed in a variety of human cancers, and involved in cell adhesion, growth, migration, invasion, and survival. However, the expression and function of HepaCAM in prostate cancer are still unknown.METHODS. HepaCAM expression has been detected by RT-PCR, Western blotting and immunohistochemistry staining in prostate cell lines RWPE-1, LNCap, DU145, PC3, and in 75 human prostate tissue specimens, respectively. Meanwhile, the cell proliferation ability was detected by WST-8 assay. The role of HepaCAM in prostate cancer cell migration and invasion was examined by wound healing and transwell assay. And flow cytometry was used to observe the apoptosis of prostate cancer cells. Then we detected changes of Androgen Receptor translocation and ERK signaling using immunofluorescence staining and western blot after overexpression of HepaCAM.RESULTS. The HepaCAM expression was significantly down-regulated in prostate cancer tissues and undetected in prostate cancer cells. However, the low HepaCAM expression was not statistically associated with clinicopathological characteristics of prostate cancer. Overexpression of HepaCAM in prostate cancer cells decreased the cell proliferation, migration and invasion, and induced the cell apoptosis. Meanwhile, HepaCAM prevented the androgen receptor translocation from the cytoplasm to the nucleus and down-regulated the MAPK/ERK signaling.CONCLUSION. Our results suggested that HepaCAM acted as a tumor suppressor in prostate cancer. HepaCAM inhibited cell viability and motility which might be through suppressing the nuclear translocation of Androgen Receptor and down-regulating the ERK signaling. Therefore, it was indicated that HepaCAM may be a potential therapeutic target for prostate cancer. (C) 2014Wiley Periodicals, Inc.