title: Repression of engrailed 2 inhibits the proliferation and invasion of human bladder cancer in vitro and in vivo.
abstract: Engrailed 2 (EN2) is a member of the homeobox gene family. Many studies suggest that overexpression of EN2 protein may be associated with tumor development, including bladder cancer (BC). However, to date, the mechanisms of how EN2 functions to promote BC progression remain elusive. The present study introduced RNAi to silence the expression of EN2 in BC cell lines. In vitro invasion and migration assays and in vivo experiments were carried out to examine the functions of EN2 in BC invasion and metastasis. The results of the present study indicated that EN2 was significantly expressed in BC cells. Ectopic expression of EN2 in normal urothelial cells significantly enhanced cellular proliferation and invasion, but inhibited cellular apoptosis. EN2 knockdown significantly promoted cell cycle arrest and apoptosis of BC cells with inhibition of proliferation and invasion in vitro as well as EN2 knockdown decreased the tumor growth of BC. The tumor growth was decreased by regulation of the cell cycle, apoptosis and epithelial-mesenchymal transition-related proteins, with inhibition of metastasis to the liver and lung in vivo. Furthermore, EN2 knockdown significantly decreased the levels of pAkt-473, pAkt-308 and phosphatidylinositol 3-kinase (PI3K), whereas EN2 knockdown increased the expression of PTEN in vitro. Taken together, EN2 may be a candidate oncogene in BC by activating the PI3K/Akt pathway and inhibiting PTEN, and may be a potential therapeutic target for the treatment of BC.
authors: Department of Urology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China.
authors: Yunfei
authors: Y
authors: Li
authors: Department of Obstetrics and Gynecology, Guangdong Women and Children's Hospital, Guangzhou, Guangdong 511400, P.R. China.
authors: Haitao
authors: H
authors: Liu
authors: Department of Urology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China.
authors: Caiyong
authors: C
authors: Lai
authors: Department of Urology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China.
authors: Zexuan
authors: Z
authors: Su
authors: Department of Urology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China.
authors: Baoli
authors: B
authors: Heng
authors: Department of Pathology, Yuebei People's Hospital, Shaoguan, Guangdong 512026, P.R. China.
authors: Shuangquan
authors: S
authors: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D019459:Urothelium / Q000378:metabolism*; D000099266:Engrailed 2 Protein
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051059:PTEN Phosphohydrolase; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D000099266:Engrailed 2 Protein; C494929:PTEN protein, human