title: NDRG1/Cap43/Drg-1 may predict tumor angiogenesis and poor outcome in patients with lung cancer.
abstract: OBJECTIVE
  Expression of N-myc downstream-regulated gene 1 (NDRG1)/Cap43 is a prognostic indicator of human malignancies according to the tumor type in which it occurs. We investigated how NDRG1/Cap43 could affect tumor growth and angiogenesis in non-small-cell lung cancer (NSCLC) in vivo using an animal experimental model, and also how it could affect tumor angiogenesis and prognosis in NSCLC patients.
  
  
  RESULTS
  Knockdown of NDRG1/Cap43 in lung cancer cells using a specific small interfering RNA resulted in growth rates in culture that were similar to those of counterpart control cells, but decreased tumor growth rates in vivo markedly. Stable NDRG1/Cap43 knockdown did not induce consistent changes in the expression of Epidermal growth factor receptor (EGFR) family proteins and c-Met in two human lung cancer cell lines in vitro. However, cell lines with NDRG1/Cap43 knockdown showed markedly decreased production of the potent angiogenic factors vascular endothelial growth factor-A and interleukin-8. Cells with knockdown of NDRG1/Cap43 showed marked reduction of tumor-induced angiogenesis. Using immunohistochemistry, we examined 182 surgically resected specimens of NSCLC for expression of NDRG1/Cap43 and tumor angiogenesis. High microvessel density in the tumor was significantly associated with nuclear positivity for NDRG1/Cap43 in both adenocarcinoma (p = 0.003) and squamous cell carcinoma (p=0.041). For both adenocarcinoma (p = 0.031) and squamous cell carcinoma (p=0.034), the survival curve of patients negative for nuclear NDRG1/Cap43 expression differed significantly from that of patients who were positive.
  
  
  CONCLUSIONS
  Therefore, the expression of NDRG1/Cap43 may be predictive of tumor angiogenesis and poor prognosis in NSCLC.
authors.affiliation: Department of Internal Medicine, Division of Respirology, Neurology, and Rheumatology, Kurume University School of Medicine, Kurume, Japan. azuma@med.kurume-u.ac.jp
authors.forename: Koichi
authors.initials: K
authors.lastname: Azuma
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kawahara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hattori
authors.forename: Tomoki
authors.initials: T
authors.lastname: Taira
authors.forename: Junji
authors.initials: J
authors.lastname: Tsurutani
authors.forename: Kosuke
authors.initials: K
authors.lastname: Watari
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Shibata
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Murakami
authors.forename: Shinzo
authors.initials: S
authors.lastname: Takamori
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ono
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
authors.forename: Takashi
authors.initials: T
authors.lastname: Yanagawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
authors.forename: Michihiko
authors.initials: M
authors.lastname: Kuwano
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000401:mortality* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000401:mortality / Q000473:pathology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D016209:Interleukin-8 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000098:blood supply / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D066246:ErbB Receptors; D016209:Interleukin-8; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C467484:VEGFA protein, human; C512478:EGFR protein, human