From U Michigan: Vitamin D receptor in lung adenocarcinoma

http://www.ncbi.nlm.nih.gov/pubmed/22564539

Lung Cancer. 2012 May 5. [Epub ahead of print]

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

Kim SH, Chen G, King AN, Jeon CK, Christensen PJ, Zhao L, Simpson RU, Thomas DG, Giordano TJ, Brenner DE, Hollis B, Beer DG, Ramnath N.

Source

Division of Medical Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, United States; College of Pharmacy, Ajou University, Suwon, Republic of Korea.

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 lungadenocarcinoma (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.