title: ALKBH3, a human AlkB homologue, contributes to cell survival in human non-small-cell lung cancer.
abstract: BACKGROUND
  We have demonstrated for the first time that a novel human AlkB homologue, ALKBH3, contributes to prostate cancer development, but its clinical and biological roles in lung cancer remain unclear.
  
  
  METHODS
  Expression of both mRNA and protein of PCA-1 was examined by RT-PCR and western blotting. We also assessed association with senescence and in vivo ALKBH3 treatment on orthotopic tumour cell inoculation, and analysed it clinicopathologically.
  
  
  RESULTS
  We have since found novel biological roles for ALKBH3 in human lung cancers, particularly in adenocarcinoma. Our immunohistochemical analysis of human adenocarcinomas and squamous cell carcinomas of the lung not only showed overexpression of ALKBH3 in these tumours but the percentage of cells positive for ALKBH3 also correlated statistically to recurrence-free survival in adenocarcinoma. Knockdown of ALKBH3 by siRNA transfection induced expression of p21(WAF1/Cip1) and p27(Kip1) in the human lung adenocarcinoma cell line A549, resulting in cell cycle arrest, senescence and strong suppression of cell growth in vitro. In vivo, peritoneal tumour growth and dissemination was inhibited in nude mice, previously inoculated with the A549 cell line, by intraperitoneal injection of ALKBH3 siRNA + atelocollagen, as demonstrated by the reduction in both number and diameter of tumours developing in the peritoneum.
  
  
  CONCLUSIONS
  We suggest that ALKBH3 contributes significantly to cancer cell survival and may be a therapeutic target for human adenocarcinoma of the lung.
authors.affiliation: Second Department of Internal Medicine, Nara Medical University School of Medicine, Shijo-cho, Kashihara, Nara 634-8521, Japan. m-tasaki@naramed-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Tasaki
authors.forename: K
authors.initials: K
authors.lastname: Shimada
authors.forename: H
authors.initials: H
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Tsujikawa
authors.forename: N
authors.initials: N
authors.lastname: Konishi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000071498:AlkB Homolog 1, Histone H2a Dioxygenase; D000071500:AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics / Q000502:physiology*; D049308:Dioxygenases / Q000235:genetics / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000494:pharmacology; D017385:Sequence Homology; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; D049308:Dioxygenases; C486439:ALKBH3 protein, human; D000071500:AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase; C499236:ALKBH1 protein, human; D000071498:AlkB Homolog 1, Histone H2a Dioxygenase; D045643:DNA Repair Enzymes