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Lung Cancer. 2012 Aug;77(2):265-71. doi: 10.1016/j.lungcan.2012.04.010. Epub 2012 May 6.

Characterization of vitamin D receptor (VDR) in lung adenocarcinoma.

Author information

1
Division of Medical Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, USA.

Abstract

PURPOSE:

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).

EXPERIMENTAL DESIGN:

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.

PMID:
22564539
PMCID:
PMC3396768
DOI:
10.1016/j.lungcan.2012.04.010
[Indexed for MEDLINE]
Free PMC Article
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