title: Oncogenic but non-essential role of N-myc downstream regulated gene 1 in the progression of esophageal squamous cell carcinoma.
abstract: N-myc downstream regulated gene 1 (NDRG1/Cap43/Drg-1) has previously been shown to be dysregulated in esophageal squamous cell carcinoma (ESCC). In this study, we investigated the role of NDRG1 in the neoplastic progression of ESCC using ectopic gain-of-function and loss-of-function approaches. Stable transfectants of the KYSE30 ESCC cell line with altered NDRG1 levels were generated by lentiviral transduction. Although no measurable effects on in vitro cell proliferation were observed with altered NDRG1 expression, the ectopic overexpression of NDRG1 was positively linked to recognized markers of metastasis, angiogenesis and apoptotic evasion. Accordingly, in the nude mouse xenograft model system, NDRG1 overexpression promoted the in vivo growth of KYSE30 derived xenografts, which could be attributed to the reduced apoptotic and enhanced angiogenic activities associated with this gene. These processes were mediated in part by increased NFκB activity in NDRG1 overexpressing cells. Nevertheless, no significant phenotypic changes were observed in response to NDRG1 knock-down, suggesting that this gene might not be essential for the neoplastic progression of ESCC. Taken together, our results suggest that NDRG1 may play positive but dispensable roles in the progression of esophageal squamous cell carcinoma.
authors.affiliation: Division of Medical Biochemistry, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Bracher-Manecke
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Zhao
authors.forename: Neil H
authors.initials: NH
authors.lastname: Davies
authors.forename: Lanping
authors.initials: L
authors.lastname: Zhou
authors.forename: Runna
authors.initials: R
authors.lastname: Ai
authors.forename: Lisa
authors.initials: L
authors.lastname: Oliver
authors.forename: Francois
authors.initials: F
authors.lastname: Vallette
authors.forename: Denver T
authors.initials: DT
authors.lastname: Hendricks
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D014183:Transplantation, Heterologous; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D018925:Chemokines; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D000099259:N-myc Downstream-Regulated Gene 1 Protein