25-Hydroxyvitamin D3-1α-hydroxylase and vitamin D receptor gene expression in human colonic mucosa is elevated during early cancerogenesis

Cross, Heide S.; Bareis, Petra; Hofer, Harald; Bischof, Martin; Bajna, Erika; Kriwanek, Stefan; Bonner, Elisabeth; Peterlik, Meinrad

doi:10.1016/s0039-128x(00)00153-7

Cited by 203 publications

(137 citation statements)

References 13 publications

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“…The immunofluorescence analysis supports our previous data Cross et al 2001) that CYP27B1 expression is elevated in tumor tissue compared with normal colon mucosa during early stages of colon tumor progression. However, high-grade un- differentiated adenocarcinomas are devoid of CYP27B1 expression except in areas with preserved differentiated structures.…”

supporting

confidence: 89%

25-Hydroxyvitamin D₃-1α-hydroxylase Expression in Normal and Malignant Human Colon

Bises

Kállay

Weiland

et al. 2004

J Histochem Cytochem.

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118

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S U M M A R Y 1,25-dihydroxyvitamin D 3 has anti-mitotic, pro-differentiating, and proapoptotic activity in tumor cells. We demonstrated that the secosteroid can be synthesized and degraded not only in the kidney but also extrarenally in intestinal cells. Evaluation of 1,25-dihydroxyvitamin D 3 -synthesizing CYP27B1 hydroxylase mRNA (real-time PCR) and protein (immunoblotting, immunofluorescence) showed enhanced expression in high-to medium-differentiated human colon tumors compared with tumor-adjacent normal mucosa or with colon mucosa from non-cancer patients. In high-grade undifferentiated tumor areas expression was lost. Many cells co-expressed CYP27B1 and the vitamin D receptor. We suggest that autocrine/paracrine antimitotic activity of 1,25-dihydroxyvitamin D 3 could prevent intestinal tumor formation and progression. An adequate 1,25-D 3 serum level is essential to maintain calcium homeostasis. Because of the hormone's anti-mitotic, pro-differentiating, pro-apoptotic activity, it has also been suggested to provide protection against tumor progression (Lamprecht and Lipkin 2003). However, treatment of tumor patients with 1,25-D 3 or with synthetic vitamin D analogues is not feasible due to the hypercalcemic effect at the pharmacological (nanomolar) doses necessary to achieve antimitotic action. Recently, another physiological link between vitamin D and cancer prevention and/or therapy has been found. In addition to the kidney, several other tissues express enzymes necessary for vitamin D synthesis. We were the first to demonstrate that human colonocytes in culture are able to synthesize 1,25-D 3 from 25-D 3 (Cross et al. 1997) and that in freshly isolated colon tumor cells a wide spectrum of vitamin D metabolites is present ). Our further studies by semiquantitative RT-PCR showed increasing levels of CYP27B1 and of VDR mRNA during early colon tumor progression . CYP27B1 mRNA was overexpressed also in cervical, breast, and ovarian carcinomas compared with normal tissue (Friedrich et al. 2003). This suggested to us an autocrine/paracrine protective effect of 1,25-D 3 synthesized in colon tumor cells during premalignancy and early malignancy. In late-stage high-grade colon cancer there is apparent failure of this protective system ). However, with present methodology it is not possible to verify this by measuring tissue accumulation of 1,25-D 3 .In view of our preliminary observations and the fact that the expression level of CYP27B1 seems to be related to the level of cell differentiation, at least in human colon tumor cell cultures (Bareis et al.

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supporting

confidence: 89%

25-Hydroxyvitamin D₃-1α-hydroxylase Expression in Normal and Malignant Human Colon

Bises

Kállay

Weiland

et al. 2004

J Histochem Cytochem.

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118

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“…However, additional data suggest that this action may, at least in part, be mediated through VDR signaling. It has been shown previously (12) that VDR is an estrogen target gene and that expression of VDR is decreasing in high-grade (poorly differentiated or undifferentiated) colon tumors (13). Low vitamin D intake is associated with colon cancer both in humans (14) and in rodents (15).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, evidence suggests that the chemopreventive effects of estrogen may, at least in part, be mediated through vitamin D receptor (VDR) signaling. VDR is a known estrogen-responsive gene (12) and colonocytes express VDR at relatively high levels; however, the expression of VDR decreases in the adenoma-carcinoma sequence (13). Low vitamin D intake is associated with colon cancer in humans (14) and rodents (15) and vitamin D supplementation decreases tumor load in Apc Min−/+ mice (16).…”

mentioning

confidence: 99%

Chemoprevention of Colorectal Neoplasia by Estrogen: Potential Role of Vitamin D Activity

Protiva

Cross

Hopkins

et al. 2009

Cancer Prevention Research

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Postmenopausal hormone replacement therapy lowers colon cancer incidence. In humans, the mechanism is unknown, but animal models suggest that it may involve activation of the vitamin D receptor (VDR) pathway.The aims of our study were to determine whether estrogen intervention affects global gene expression in rectal mucosal biopsies and whether vitamin D-related genes are affected.Estradiol was given to raise serum estradiol to premenopausal levels in 10 postmenopausal women under close nutritional control. Primary end points were expression of VDR, CYP24A1, CYP27B1, and E-cadherin in rectal mucosa by reverse transcription-PCR and examining response to estradiol by genome-wide arrays. Responses in gene expression in rectal biopsies to estrogen were determined in each subject individually and compared with a human estrogen response gene array database and a custom array in vitro-generated database.Cluster analysis showed that subjects maintained their overall gene expression profile and that interindividual differences were greater than intraindividual differences after intervention. Eight of 10 subjects showed significant enrichment in estrogen-responsive genes. Gene array group analysis showed activation of the VDR pathway and down-regulation of inflammatory and immune signaling pathways. Reverse transcription-PCR analysis showed significant up-regulation of VDR and E-cadherin, a downstream target of vitamin D action.These data suggest that the chemopreventive action of hormone replacement therapy on colon neoplasia results, at least in part, from changes in vitamin D activity. Evaluation of gene arrays is useful in chemopreventive intervention studies in small groups of subjects.

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“…VDR is expressed in many tissues, including human colon tissue (16,17). The presence of CYP27B1, CYP24A1, and VDR suggest that vitamin D might interact with colon tissue, as will be explained in the next section.…”

Section: Vitamin D: Metabolism and Mechanism Of Actionmentioning

confidence: 92%

“…The first hydroxylation step occurs in the liver by the enzyme 25-hydroxylase, which yields 25-hydroxyvitamin D (25(OH)D). The second hydroxylation is performed by another enzyme of the cytochrome P450 (CYP) system, CYP27B1, which is present in the kidney but also in human colon tissue (15)(16)(17). Calcitriol is inactivated by different enzymes including CYP24A1, which is overexpressed in colon cancer cells (18,19).…”

Section: Vitamin D: Metabolism and Mechanism Of Actionmentioning

confidence: 99%

Vitamin D, Inflammation, and Colorectal Cancer Progression: A Review of Mechanistic Studies and Future Directions for Epidemiological Studies

Harten-Gerritsen

Balvers

Witkamp

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Survival from colorectal cancer is positively associated with vitamin D status. However, whether this association is causal remains unclear. Inflammatory processes may link vitamin D to colorectal cancer survival, and therefore investigating inflammatory markers as potential mediators may be a valuable next step. This review starts with an overview of inflammatory processes suggested to be involved in colorectal cancer progression and regulated by vitamin D. Next, we provide recommendations on how to study inflammatory markers in future epidemiologic studies on vitamin D and colorectal cancer survival. Mechanistic studies have shown that calcitriol-active form of vitamin Dinfluences inflammatory processes involved in cancer progression, including the enzyme cyclooxygenase 2, the NF-kB pathway, and the expression of the cytokines TNFa, IL1b, IL6, IL8, IL17, and TGFb1. Based on this and taking into account methodologic issues, we recommend to include analysis of specific soluble peptides and proteins, such as cytokines, in future epidemiologic studies on this issue. Vitamin D and the markers should preferably be measured at multiple time points during disease progression or recovery and analyzed using mediation analysis. Including these markers in epidemiologic studies may help answer whether inflammation mediates a causal relationship between vitamin D and colorectal cancer survival. Cancer Epidemiol Biomarkers Prev; 24(12); 1820-8. Ó2015 AACR.

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25-Hydroxyvitamin D3-1α-hydroxylase and vitamin D receptor gene expression in human colonic mucosa is elevated during early cancerogenesis

Cited by 203 publications

References 13 publications

25-Hydroxyvitamin D₃-1α-hydroxylase Expression in Normal and Malignant Human Colon

25-Hydroxyvitamin D₃-1α-hydroxylase Expression in Normal and Malignant Human Colon

Chemoprevention of Colorectal Neoplasia by Estrogen: Potential Role of Vitamin D Activity

Vitamin D, Inflammation, and Colorectal Cancer Progression: A Review of Mechanistic Studies and Future Directions for Epidemiological Studies

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25-Hydroxyvitamin D3-1α-hydroxylase and vitamin D receptor gene expression in human colonic mucosa is elevated during early cancerogenesis

Cited by 203 publications

References 13 publications

25-Hydroxyvitamin D3-1α-hydroxylase Expression in Normal and Malignant Human Colon

25-Hydroxyvitamin D3-1α-hydroxylase Expression in Normal and Malignant Human Colon

Chemoprevention of Colorectal Neoplasia by Estrogen: Potential Role of Vitamin D Activity

Vitamin D, Inflammation, and Colorectal Cancer Progression: A Review of Mechanistic Studies and Future Directions for Epidemiological Studies

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25-Hydroxyvitamin D₃-1α-hydroxylase Expression in Normal and Malignant Human Colon

25-Hydroxyvitamin D₃-1α-hydroxylase Expression in Normal and Malignant Human Colon