Characterization of vitamin D receptor (VDR) in lung adenocarcinoma.
Characterization of vitamin D receptor (VDR) in lung adenocarcinoma.
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DOI：
10.1016/j.lungcan.2012.04.010
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发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
Ramnath N
中科院分区：
文献类型：
--
作者：
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
1α，25-二羟基维生素D3（1，25-D3，骨化三醇，维生素D的活性形式）的抗增殖作用由核维生素D受体（VDR）介导。在本研究中，我们的特点VDR表达在肺腺癌（AC）。我们使用定量实时PCR（qRT-PCR）检测了100例接受肺AC手术的患者的VDR mRNA表达。在这些患者的一个子集（n = 89），我们检查VDR蛋白表达免疫组化。我们还检查了VDR蛋白表达与循环血清25-羟基维生素D3（25-D3）和1，25-D3水平的相关性。使用VDR mRNA高表达（SKLU-1）和低表达（A549）的肺癌细胞系检查1，25-D3的抗增殖作用和细胞周期阻滞。在调整年龄、性别、疾病分期和肿瘤分级后，较高的VDR表达与较长的生存期相关（HR 0.73，95% CI 0.58-0.91）。血清1，25-D3与肿瘤VDR蛋白表达呈正相关（r = 0.38）。与低VDR表达细胞系相比，在高VDR表达细胞系中观察到更大的1，25-D3抗增殖作用;这些作用对应于G1细胞周期阻滞;这与参与S期进入的细胞周期蛋白D1、S期激酶蛋白2（Skp 2）、视网膜母细胞瘤（Rb）和微小染色体维持2（MCM 2）蛋白的下降有关。肺AC中VDR表达的增加与存活率的改善相关。这可能与高VDR表达肿瘤的较低增殖状态和G1期阻滞有关。
The anti-proliferative effects of 1α,25-dihydroxyvitamin D3 (1,25-D3, 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). 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 D3 (25-D3) and 1,25-D3. The antiproliferative effects and cell cycle arrest of 1,25-D3 were examined using lung cancer cell lines with high (SKLU-1) as well as low (A549) expression of VDR mRNA. 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-D3 and tumor VDR protein expression. A greater anti-proliferative effect of 1,25-D3 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. 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.
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影响因子：
4.8
作者：
Hedlund, TE;Moffatt, KA;Miller, GJ
通讯作者：
Miller, GJ
影响因子：
3.6
作者：
Kaiser, U;Schilli, M;Havemann, K
通讯作者：
Havemann, K
影响因子：
64.8
作者：
Rachez, C;Lemon, BD;Freedman, LP
通讯作者：
Freedman, LP
影响因子：
11.5
作者：
Fakih, Marwan G.;Trump, Donald L.;Johnson, Candance S.
通讯作者：
Johnson, Candance S.
DOI：
10.4049/jimmunol.181.10.7090
发表时间：
2008-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hansdottir S;Monick MM;Hinde SL;Lovan N;Look DC;Hunninghake GW
通讯作者：
Hunninghake GW