Vitamin D Receptor Expression in Normal, Premalignant, and Malignant Human Lung Tissue

Menezes, Ravi; Cheney, Richard; Husain, Aliya N.; Tretiakova, Maria; Loewen, Gregory; Johnson, Candace S.; Jayaprakash, Vijay; Moysich, Kirsten B.; Salgia, Ravi; Reid, Mary E.

doi:10.1158/1055-9965.epi-07-2713

Cited by 80 publications

(73 citation statements)

References 16 publications

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“…This means that the tumours would be less responsive to vitamin D, thus preventing its antitumour activities. Our immunohistochemistry results concur with a larger study on the expression of VDR in normal, premalignant and malignant bronchial tissue [6]. Furthermore, they are also consistent with genetic epidemiology work that shows that VDR polymorphisms that lead to reduced VDR function are associated with malignancy in general [35].…”

Section: Discussionsupporting

confidence: 91%

“…An additional 4-min haematoxylin counterstain was used in the anti-DBP protocol. The VDR protocol was adapted from that published for lung tissue [6] and the DBP protocol from that published for kidney tissue [17]. Positive controls were kidney tissue (VDR) and liver (DBP); positive staining was determined by a pathologist using standard semiquantitative techniques that grade intensity of staining [18].…”

Section: Prognostic Effect Of Serum Markers Of the Vitamin D Axismentioning

confidence: 99%

“…Once inside the cell, vitamin D dissociates from DBP and then undergoes a series of reactions that enable interaction with the vitamin D receptor (VDR), a process illustrated in our previous work [5]. There is some suggestion that VDR expression is reduced in lung cancer [6], implying that vitamin D will be less able to exert its antitumour effects, such that other aspects of the vitamin D axis could be more important. produced in the liver and located predominantly in serum.…”

mentioning

confidence: 95%

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Circulating DBP level and prognosis in operated lung cancer: an exploration of pathophysiology

Turner¹,

McGowan²,

Millen³

et al. 2012

Eur Respir J

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Vitamin D stimulates transcription of antiangiogenic and apoptotic factors that may suppress tumours, while vitamin D binding protein (DBP) may be a biomarker in murine lung cancer models. We sought to ascertain whether the vitamin D axis is altered in lung cancer or influences prognosis.148 lung cancer patients, 68 other intrathoracic cancer patients and 33 noncancer controls were studied for up to 5 yrs. Circulating DBP and vitamin D levels were compared between groups and their effect on survival assessed by Cox regression analysis. Expression of DBP and vitamin D receptor (VDR) was examined in lung cancer cell lines and in normal and tumour lung tissue by Western blot and immunohistochemistry.Low serum DBP levels predicted lung cancer-specific death (p50.04), and DBP was poorly expressed in lung cancer cells on Western blot and immunohistochemistry. Vitamin D did not predict cancer survival and VDR expression was variable in tumours.Preservation of serum DBP is a significant independent factor associated with better cancer outcome in operated lung cancer patients. Given the established role of DBP in macrophage activation and clearance of abnormal cells, further study on its involvement in lung cancer is merited.

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Section: Discussionsupporting

confidence: 91%

Section: Prognostic Effect Of Serum Markers Of the Vitamin D Axismentioning

confidence: 99%

mentioning

confidence: 95%

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Circulating DBP level and prognosis in operated lung cancer: an exploration of pathophysiology

Turner¹,

McGowan²,

Millen³

et al. 2012

Eur Respir J

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“…The balance between the cellular compartments (nuclear/cytoplasmic) is probably relevant to the regulatory actions of vitamin D. More pronounced cytoplasmic VDR staining could indicate an 'escape' of parathyroid adenoma cells from homeostatic surveillance and growth control, especially if the regulatory mechanisms depended on ligand-activated receptor activity (29). Such alterations in cytoplasmic and nuclear VDR staining have also been reported in other neoplasms (30,31,32).…”

Section: Discussionmentioning

confidence: 82%

Simultaneous expression analysis of vitamin D receptor, calcium-sensing receptor, cyclin D1, and PTH in symptomatic primary hyperparathyroidism in Asian Indians

Varshney

Bhadada

Saikia

et al. 2013

European Journal of Endocrinology

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Background: To explore underlying molecular mechanisms in the pathogenesis of symptomatic sporadic primary hyperparathyroidism (PHPT). Materials and methods: Forty-one parathyroid adenomas from patients with symptomatic PHPT and ten normal parathyroid glands either from patients with PHPT (nZ3) or from euthyroid patients without PHPT during thyroid surgery (nZ7) were analyzed for vitamin D receptor (VDR), calcium-sensing receptor (CASR), cyclin D1 (CD1), and parathyroid hormone (PTH) expressions. The protein expressions were assessed semiquantitatively by immunohistochemistry, based on percentage of positive cells and staining intensity, and confirmed by quantitative real-time PCR. Results: Immunohistochemistry revealed significant reductions in VDR (both nuclear and cytoplasmic) and CASR expressions and significant increases in CD1 and PTH expressions in adenomatous compared with normal parathyroid tissue. Consistent with immunohistochemistry findings, both VDR and CASR mRNAs were reduced by 0.36-and 0.45-fold change (P!0.001) and CD1 and PTH mRNAs were increased by 9.4-and 17.4-fold change respectively (P!0.001) in adenomatous parathyroid tissue. PTH mRNA correlated with plasma PTH (rZ0.864; P!0.001), but not with adenoma weight, while CD1 mRNA correlated with adenoma weight (rZ0.715; P!0.001). There were no correlations between VDR and CASR mRNA levels and serum Ca, plasma intact PTH, or 25-hydroxyvitamin D levels. In addition, there was no relationship between the decreases in VDR and CASR mRNA expressions and the increases in PTH and CD1 mRNA expressions. Conclusions: The expression of both VDR and CASR are reduced in symptomatic PHPT in Asian Indians. In addition, CD1 expression was greatly increased and correlated with adenoma weight, implying a potential role for CD1 in adenoma growth and differential clinical expression of PHPT.

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“…VDR has been implicated as a biomarker for lung cancer progression. 47 and its expression in lung cancer cells is increased in response to DNA damaging agents. 29 In K-ras mutated colon cancer cells, VDR suppression leads to cell death mediated by p38 MAP kinase.…”

Section: The Vitamin D Receptor (Vdr) Sensitizes Pancreatic Cancer Cementioning

confidence: 99%

A synthetic lethal screen identifies the Vitamin D receptor as a novel gemcitabine sensitizer in pancreatic cancer cells

2014

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Vitamin D Receptor Expression in Normal, Premalignant, and Malignant Human Lung Tissue

Cited by 80 publications

References 16 publications

Circulating DBP level and prognosis in operated lung cancer: an exploration of pathophysiology

Circulating DBP level and prognosis in operated lung cancer: an exploration of pathophysiology

Simultaneous expression analysis of vitamin D receptor, calcium-sensing receptor, cyclin D1, and PTH in symptomatic primary hyperparathyroidism in Asian Indians

A synthetic lethal screen identifies the Vitamin D receptor as a novel gemcitabine sensitizer in pancreatic cancer cells

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