title: Downregulation of bone morphogenetic protein receptor 2 promotes the development of neuroblastoma.
abstract: Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. In this study, we examined the expression of bone morphogenetic protein receptor 2 (BMPR2) in primary NB and adjacent non-tumor samples (adrenal gland). BMPR2 expression was significantly downregulated in NB tissues, particularly in high-grade NB, and was inversely related to the expression of the NB differentiation markers ferritin and enolase. The significance of the downregulation was further explored in cultured NB cells. While enforced expression of BMPR2 decreased cell proliferation and colony-forming activity, shRNA-mediated knockdown of BMPR2 led to increased cell growth and clonogenicity. In mice, NB cells harboring BMPR2 shRNA showed significantly increased tumorigenicity compared with control cells. We also performed a retrospective analysis of NB patients and identified a significant positive correlation between tumor BMPR2 expression and overall survival. These findings suggest that BMPR2 may play an important role in the development of NB.
authors.affiliation: Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects, and Key Laboratory of Neonatal Diseases, Ministry of Health, Shanghai, PR China.
authors.forename: Ximao
authors.initials: X
authors.lastname: Cui
authors.affiliation: Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, Jiangsu, PR China.
authors.forename: Yili
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Fudan University Shanghai Cancer Center, Shanghai, PR China.
authors.forename: Deshui
authors.initials: D
authors.lastname: Jia
authors.affiliation: Fudan University Shanghai Cancer Center, Shanghai, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Department of General Surgery, Jiangxi Children's Hospital, Nanchang, Jiangxi, PR China.
authors.forename: Shouhua
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects, and Key Laboratory of Neonatal Diseases, Ministry of Health, Shanghai, PR China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Long
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects, and Key Laboratory of Neonatal Diseases, Ministry of Health, Shanghai, PR China. Electronic address: dongrui_1982@126.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Dong
authors.affiliation: Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defects, and Key Laboratory of Neonatal Diseases, Ministry of Health, Shanghai, PR China. Electronic address: kuirand@hotmail.com.
authors.forename: Kuiran
authors.initials: K
authors.lastname: Dong
mesh_terms: D000293:Adolescent; D000818:Animals; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002648:Child; D015536:Down-Regulation; D005260:Female; D005293:Ferritins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009447:Neuroblastoma / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011379:Prognosis; D034741:RNA, Small Interfering / Q000378:metabolism; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D034741:RNA, Small Interfering; D005293:Ferritins; C498218:BMPR2 protein, human; C498219:Bmpr2 protein, mouse; D052006:Bone Morphogenetic Protein Receptors, Type II; D010751:Phosphopyruvate Hydratase
keywords: BMPR2; Cancer; Neuroblastoma; Pediatrics; Proliferation