title: Potential role of a navigator gene NAV3 in colorectal cancer.
abstract: BACKGROUND
  The recently described navigator proteins have a multifaceted role in cytoskeletal dynamics. We report here on the relevance of one of them, navigator 3 (NAV3), in colorectal cancer (CRC).
  
  
  METHODS
  We analysed changes in chromosome 12 and NAV3 copy number in CRC/adenoma samples of 59 patients and in 6 CRC cell lines, using fluorescence in situ hybridisation, loss of heterozygosity, and array-CGH. NAV3 target genes were identified by siRNA depletion, expression arrays, and immunohistochemistry.
  
  
  RESULTS
  NAV3 deletion and chromosome 12 polysomy were detected in 30 and 70% of microsatellite stability (MSS) carcinomas, in 23 and 30% of adenomas and in four of six CRC cell lines. NAV3 amplification was found in 25% of MSS samples. NAV3 alterations correlated with lymph node metastasis. In normal colon cells, NAV3 silencing induced upregulation of interleukin 23 receptor (IL23R) and gonadotropin releasing hormone receptor. In MSS and microsatellite instability tumours, IL23R immunoreactivity correlated with Dukes' staging and lymph node metastases, whereas nuclear beta-catenin correlated with lymph node metastases only.
  
  
  CONCLUSIONS
  NAV3 copy number changes are frequent in CRC and in adenomas, and upregulation of IL23R, following NAV3 silencing, strongly correlates with Dukes' staging and lymph node metastases. This suggests that NAV3 has a role in linking tissue inflammation to cancer development in the colon.
authors.affiliation: Department of Dermatology and Allergology, University of Helsinki and Helsinki University Central Hospital, PO Box 160, FI-00029 Helsinki, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Carlsson
authors.forename: A
authors.initials: A
authors.lastname: Ranki
authors.forename: L
authors.initials: L
authors.lastname: Sipilä
authors.forename: L
authors.initials: L
authors.lastname: Karenko
authors.forename: W M
authors.initials: WM
authors.lastname: Abdel-Rahman
authors.forename: K
authors.initials: K
authors.lastname: Ovaska
authors.forename: L
authors.initials: L
authors.lastname: Siggberg
authors.forename: U
authors.initials: U
authors.lastname: Aapola
authors.forename: R
authors.initials: R
authors.lastname: Ässämäki
authors.forename: V
authors.initials: V
authors.lastname: Häyry
authors.forename: K
authors.initials: K
authors.lastname: Niiranen
authors.forename: M
authors.initials: M
authors.lastname: Helle
authors.forename: S
authors.initials: S
authors.lastname: Knuutila
authors.forename: S
authors.initials: S
authors.lastname: Hautaniemi
authors.forename: P
authors.initials: P
authors.lastname: Peltomäki
authors.forename: K
authors.initials: K
authors.lastname: Krohn
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008565:Membrane Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000235:genetics*; D034741:RNA, Small Interfering / Q000032:analysis; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: C484844:GNRHR protein, human; C515500:IL23R protein, human; D008565:Membrane Proteins; C464453:NAV3 protein, human; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D018123:Receptors, Interleukin; D011966:Receptors, LHRH