title: Characterization of vitamin D receptor (VDR) in lung adenocarcinoma.
abstract: OBJECTIVE
  The anti-proliferative effects of 1α,25-dihydroxyvitamin D(3) (1,25-D(3), calcitriol, the active form of vitamin D) are mediated by the nuclear vitamin D receptor (VDR). In the present study, we characterized VDR expression in lung adenocarcinoma (AC).
  
  
  METHODS
  We examined VDR mRNA expression using a quantitative real-time PCR (qRT-PCR) in 100 patients who underwent surgery for lung AC. In a subset of these patients (n=89), we examined VDR protein expression using immunohistochemistry. We also examined the association of VDR protein expression with circulating serum levels of 25-hydroxyvitamin D(3) (25-D(3)) and 1,25-D(3). The antiproliferative effects and cell cycle arrest of 1,25-D(3) were examined using lung cancer cell lines with high (SKLU-1) as well as low (A549) expression of VDR mRNA.
  
  
  RESULTS
  Higher VDR expression correlates with longer survival after adjusting for age, sex, disease stage and tumor grade (HR 0.73, 95% CI 0.58-0.91). In addition, there was a positive correlation (r=0.38) between serum 1,25-D(3) and tumor VDR protein expression. A greater anti-proliferative effect of 1,25-D(3) was observed in high compared to low VDR-expressing cell lines; these effects corresponded to G1 cell cycle arrest; this was associated with a decline in cyclin D1, S-phase kinase protein 2 (Skp2), retinoblastoma (Rb) and minichromosome maintenance 2 (MCM2) proteins involved in S-phase entry.
  
  
  CONCLUSIONS
  Increased VDR expression in lung AC is associated with improved survival. This may relate to a lower proliferative status and G1 arrest in high VDR-expressing tumors.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, USA.
authors.forename: So Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Guoan
authors.initials: G
authors.lastname: Chen
authors.forename: Amanda N
authors.initials: AN
authors.lastname: King
authors.forename: Chae Kyung
authors.initials: CK
authors.lastname: Jeon
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Christensen
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.forename: Robert U
authors.initials: RU
authors.lastname: Simpson
authors.forename: Dafydd G
authors.initials: DG
authors.lastname: Thomas
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Giordano
authors.forename: Dean E
authors.initials: DE
authors.lastname: Brenner
authors.forename: Bruce
authors.initials: B
authors.lastname: Hollis
authors.forename: David G
authors.initials: DG
authors.lastname: Beer
authors.forename: Nithya
authors.initials: N
authors.lastname: Ramnath
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D000368:Aged; D002112:Calcifediol / Q000097:blood; D002117:Calcitriol / Q000097:blood; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
chemical_list: D018167:Receptors, Calcitriol; D002117:Calcitriol; D002112:Calcifediol