Sun Pengcheng, Sun Xinhai, Zhao Weiming, Ren Minghua, Zhang Cheng, Wang Ziqi, Xu Wanhai
Department of Urology, the Fourth Hospital of Harbin Medical University, Harbin, China.
Department of general surgery, the Fourth Hospital of Harbin Medical University, Harbin, China.
Cell Physiol Biochem. 2017;42(6):2582-2592. doi: 10.1159/000480220. Epub 2017 Aug 24.
BACKGROUND/AIMS: Lemur tyrosine kinase (LMTK)-3 is a member of the receptor tyrosine kinase (RTK) family. Abnormal expression of LMTK-3 exists in various types of cancers, especially in endocrine-resistant breast cancers; however, the precise level of expression and the biological function in prostate cancer are poorly understood.
In the present study, we determined the expression of LMTK-3 in prostate cancer using immunohistochemistry and Western blotting. We infected PC3 and LNCaP cells with lentivirus-LMTK-3 and observed the biologic characteristics of the PC3 and LNCaP cells in vitro with TUNEL, and migration and invasion assays, respectively. We also established a transplant tumor model of human prostate cancer with infected cells in 15 BALB/c-nu/nu nude mice.
LMTK-3 was expressed in prostate epithelial cells. There was a significant decline in the level of LMTK-3 expression in prostate cancers compared to normal tissues. LMTK-3 inhibited PC3 and LNCaP cell growth, migration, and invasion, and induced cell apoptosis in vitro. We also observed that LMTK-3 induced PC3 cell apoptosis in vivo. Further study showed that LMTK-3 inhibited phosphorylation of AKT and ERK, and promoted phosphorylation and activation of p38 kinase and Jun kinase (JNK).
Recombinant lentivirus with enhanced expression of LMTK-3 inhibited prostate cancer cell growth and induced apoptosis in vitro and in vivo. AKT and MAPK signaling pathways may contribute to the process.
背景/目的：狐猴酪氨酸激酶（LMTK）-3是受体酪氨酸激酶（RTK）家族的成员。LMTK-3在多种类型癌症中存在异常表达，尤其是在内分泌抵抗性乳腺癌中；然而，其在前列腺癌中的精确表达水平和生物学功能尚不清楚。
在本研究中，我们使用免疫组织化学和蛋白质印迹法测定LMTK-3在前列腺癌中的表达。我们用慢病毒-LMTK-3感染PC3和LNCaP细胞，并分别通过TUNEL、迁移和侵袭试验观察PC3和LNCaP细胞在体外的生物学特性。我们还用感染的细胞在15只BALB/c-nu/nu裸鼠中建立了人前列腺癌移植瘤模型。
LMTK-3在前列腺上皮细胞中表达。与正常组织相比，前列腺癌中LMTK-3的表达水平显著下降。LMTK-3在体外抑制PC3和LNCaP细胞的生长、迁移和侵袭，并诱导细胞凋亡。我们还观察到LMTK-3在体内诱导PC3细胞凋亡。进一步研究表明，LMTK-3抑制AKT和ERK的磷酸化，并促进p38激酶和Jun激酶（JNK）的磷酸化和激活。
增强LMTK-3表达的重组慢病毒在体外和体内均抑制前列腺癌细胞生长并诱导凋亡。AKT和MAPK信号通路可能参与了这一过程。
