Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer.

Colston, Kay W.; Hansen, Christina Mørk

doi:10.1677/erc.0.0090045

Cited by 223 publications

(196 citation statements)

References 88 publications

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“…On the other hand, it is well established that active vitamin D metabolites or analogs are efficacious in inhibiting cell proliferation and inducing cell differentiation [26][27][28][29]. Here we use an unique mouse mammary organ culture system to demonstrate the chemopreventive role of 25(OH)D 3 in DMBA-induced carcinogenesis of mouse mammary glands at its physiological concentration.…”

Section: Discussionmentioning

confidence: 99%

25-Hydroxyvitamin D3 is a natural chemopreventive agent against carcinogen induced precancerous lesions in mouse mammary gland organ culture

Xiang

Hawthorne

Vaishnav

et al. 2008

Breast Cancer Res Treat

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Despite the role of vitamin D 3 endocrine system in prevention of mammary gland transformation in animal models, use of 1,25(OH) 2 D 3 in clinical settings is precluded due to its toxicity in vivo. Therefore much effort has been placed in developing relatively non-toxic vitamin D analogs. Recently, with the discovery of the expression of 25-hydroxy vitamin D 3 1α-hydroxylase (CYP27B1) in multiple extrarenal organs, the functional role of prohormone, 25-hydroxyvitamin D 3 [25(OH) D 3 ], has been redefined. Since 25(OH)D 3 does not cause hypercalcemia and maintains relative high concentration in serum, it is possible that the prohormone can be converted to active hormone in mammary epithelial cells to provide chemopreventive effects. In the present study, we evaluated its functional significance using mouse mammary organ culture (MMOC) system. We first showed that 25(OH)D 3 1α-hydroxylase is extensively expressed in mammary ductal epithelial cells at both protein and mRNA levels, which is a prerequisite for 25(OH)D 3 to function in an autocrine/paracrine manner. However, we also observed that clotrimazol (1α-hydroxylase inhibitor) enhanced 25(OH) D 3 -induced CYP24 expression in breast cancer cells. In mammary glands derived from 1α-hydroxylase knockout mice, 25(OH)D 3 treatment in organ culture significantly induced CYP24 expression, indicating a potential direct effect of 25(OH)D 3 . In MMOC, 100-250 nM 25(OH)D 3 suppressed both ovarian hormone-dependent and -independent mammary precancerous lesions (induced by DMBA) by more than 50%, while the active hormone 1,25(OH) 2 D 3 (positive control) at 100 nM suppressed alveolar lesions by more than 80%. The inactive vitamin D 3 (negative control) at 100 nM suppressed alveolar lesions by only 20% (P > 0.05). We found that 25(OH)D 3 inhibits DMBA-induced mammary alveolar lesions (MAL) in a stage-specific manner: 25(OH)D 3 mainly inhibits the promotion stage of lesion formation. We conclude that 25(OH)D 3 could serve as a nontoxic natural chemopreventive agent for further development for breast cancer prevention.

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Section: Discussionmentioning

confidence: 99%

25-Hydroxyvitamin D3 is a natural chemopreventive agent against carcinogen induced precancerous lesions in mouse mammary gland organ culture

Xiang

Hawthorne

Vaishnav

et al. 2008

Breast Cancer Res Treat

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“…the known anticarcinogenic effects of vitamin D with regard to apoptosis, cell differentiation and proliferation and growth inhibition of human mammary epithelial cells by both 1,25(OH) 2 29,30 Confirming our a priori hypothesis, we observed in this population-based case-control study a significantly inverse association between Conditional logistic regression stratified by age and adjusted for time of blood collection.-2 Conditional logistic regression stratified by age and adjusted for time of blood collection, number of births, first-degree family history, age at menarche, duration of breast-feeding, BMI, alcohol consumption. plasma 25(OH)D and premenopausal breast cancer risk.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6] Most of the epidemiologic studies regarding breast cancer risk have assessed the effects of vitamin D only for dietary intake yielding inconsistent results. [7][8][9][10][11][12][13][14][15] However, beside dietary intake, the main source of vitamin D is cutaneous production via sun exposure.…”

mentioning

confidence: 99%

“…16,17 However, an appropriate biomarker to measure vitamin D status in humans, accounting for both vitamin D from diet and endogenous production, is 25-hydroxyvitamin [25(OH)D]. 25(OH)D is converted to 1,25-dihydroxyvitamin D [1,25(OH) 2 D], the biologically active form of vitamin D, in the liver and other tissues including breast. [18][19][20] Few studies have assessed the relationship between serum or plasma 25(OH)D and breast cancer risk.…”

mentioning

confidence: 99%

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Plasma 25‐hydroxyvitamin D and premenopausal breast cancer risk in a German case‐control study

Abbas

Chang‐Claude

Linseisen

2008

Intl Journal of Cancer

110

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Laboratory and epidemiological data have linked vitamin D to breast cancer prevention. Beside dietary intake, endogenous production of vitamin D substantially contributes to a subject's vitamin D status. Most studies, however, have assessed dietary intake only. Although differential effects of vitamin D on premenopausal and postmenopausal breast cancer have been discussed, this is the first study to investigate the association of plasma 25-hydroxyvitamin D [25(OH)D], as indicator of the overall vitamin D status, with breast cancer risk with restriction to premenopausal women only. We used data of a population-based case-control study comprising 289 cases and 595 matched controls. Information on sociodemographic and breast cancer risk factors was collected by questionnaire and plasma 25(OH)D was measured by enzyme immunoassay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. We observed a significant inverse association between breast cancer risk and plasma 25(OH)D concentrations. Compared with the lowest category (<30 nmol/L), the ORs (95% CI) for the upper categories [18][19][20] Few studies have assessed the relationship between serum or plasma 25(OH)D and breast cancer risk. [21][22][23][24][25] Of 2 small hospitalbased case-control studies in predominantly postmenopausal women, one study found a significantly inverse association 23 whereas the other study revealed no association between plasma 25(OH)D and breast cancer risk. 25 To date, 2 studies assessed the association of vitamin D metabolites with breast cancer risk with restriction to postmenopausal women only. 21,22 A study nested in the prostate, lung, colorectal and ovarian cancer screening trial reported no association between both higher plasma 25(OH)D and 1,25(OH) 2 D concentration and breast cancer risk. 22 However, a strong statistically significant inverse association between postmenopausal breast cancer risk and serum 25(OH)D was found in a large case-control study. 21 A case-control study nested in the Nurses' Health Study (NHS) is the only study that so far reported results stratified by menopausal status. 24 The authors reported a nonsignificant decrease in breast cancer risk with both higher plasma 25(OH)D and 1,25(OH) 2 D concentration for overall breast cancer risk. Stratification by menopausal status suggested an inverse association for postmenopausal women only, however power was low for their analysis in premenopausal women and risk estimates were not presented. As reviewed recently, prospective studies on dietary intake of vitamin D suggest a more pronounced effect for premenopausal breast cancer risk. 26 Furthermore, we recently reported a significant inverse association of dietary vitamin D with premenopausal breast cancer risk in the present study population. 13 To our knowledge, no study so far assessed the association of plasma 25(OH)D with restriction to premenopausal breast cancer only. Following our previous report on the association between postmenopausal breast canc...

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“…1α 25(OH) 2 D 3 also induced apoptosis through directly activate caspase effector molecules, although it is unclear whether 1, 25(OH) 2 D 3 -induced apoptosis is caspase-dependent or independent (Deeb et al, 2007). It has also reported that some breast cancer cells shows potentiate TNF alpha induced apoptosis through the death receptor pathway, which is linked to the activation of caspases and phospholipase A2 (Colston and Hansen, 2002). A novel mechanism of 1α 25(OH) 2 D 3 -mediated apoptosis in epithelial ovarian cancer cells was proposed by Jiang et al(2004), wherein they showed that 1 α 25(OH) 2 D 3 destabilizes telomerase reverse transcriptase (TERT) mRNA, therefore inducing apoptosis through telomere attrition resulting from the down-regulation of telomerase activity and it is first study which demonstrate stability of hTERT mRNA by a hormone.…”

Section: Cyp24a1mentioning

confidence: 99%

Recent Candidate Molecular Markers: Vitamin D Signaling and Apoptosis Specific Regulator of p53 (ASPP) in Breast Cancer

Patel

Patel²,

Patel³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer.

Cited by 223 publications

References 88 publications

25-Hydroxyvitamin D3 is a natural chemopreventive agent against carcinogen induced precancerous lesions in mouse mammary gland organ culture

25-Hydroxyvitamin D3 is a natural chemopreventive agent against carcinogen induced precancerous lesions in mouse mammary gland organ culture

Plasma 25‐hydroxyvitamin D and premenopausal breast cancer risk in a German case‐control study

Recent Candidate Molecular Markers: Vitamin D Signaling and Apoptosis Specific Regulator of p53 (ASPP) in Breast Cancer

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