Growth inhibition of both MCF-7 and Hs578T human breast cancer cell lines by vitamin D analogues is associated with increased expression of insulin-like growth factor binding protein-3

Article (PDF Available)inJournal of Molecular Endocrinology 20(1):157-62 · February 1998with54 Reads
Source: PubMed
The effects of two vitamin D analogues, EB1089 and CB1093, on insulin-like growth factor binding protein (IGFBP) expression have been examined in MCF-7 and Hs578T human breast cancer cell lines. Both vitamin D analogues inhibited IGF-1 stimulated growth of MCF-7 cells and enhanced the production of IGFBP-3 as determined by Western-ligand blotting. Recombinant human IGFBP-3 inhibited the growth of MCF-7 cells over the concentration range 1-235 ng/ml. Hs578T cells were unresponsive to the mitogenic effects of IGF-1 but growth was inhibited by the two vitamin D analogues. Treatment of Hs578T cells with EB1089 and CB1093 (10 nM) as well as 100 nM 9-cis retinoic acid (9-cis RA) or all-trans retinoic acid (ATRA) was associated with increased accumulation of IGFBP-3 in conditioned medium. Furthermore, cotreatment of Hs578T cells with EB1089 and 9-cis RA led to augmented effects on both inhibition of cell growth and IGFBP-3 accumulation in conditioned medium as assessed by Western ligand blotting and radioimmunoassay. These findings suggest a role for IGFBP-3 in the growth inhibitory effects of vitamin D analogues.
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Journal of Molecular Endocrinology (1998) 20, 157–162 ? 1998 Journal of Endocrinology Ltd Printed in Great Britain
0952–5041/98/020–157 $08.00/0 Accepted 13 January 1998
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Journal of Molecular Endocrinology (1998) 20, 157–162
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Journal of Molecular Endocrinology (1998) 20, 157–162
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Journal of Molecular Endocrinology (1998) 20, 157–162
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Journal of Molecular Endocrinology (1998) 20, 157–162
    • "Vitamin D has been shown to stimulate and enhance the expression of IGFBP-3 [16, 29]. In contrast, it inhibits the mitogenic effect of IGF1, attenuates the antiapoptotic effect of IGF1, and down regulates the expression of IGF1 receptors [29, 52, 53]. However in our mediation analyses, we did not observe any evidence of the indirect effects of serum 25(OH)D3 on MD through IGF1 and IGFBP3. "
    [Show abstract] [Hide abstract] ABSTRACT: Low circulating levels of vitamin D and high mammographic density (MD) have been associated with higher risk of breast cancer. Although some evidence suggested an inverse association between circulating vitamin D and MD, no studies have investigated this association among Mexican women. We examined whether serum 25−hydroxyvitamin D3 [25(OH)D3] levels were associated with MD in a cross-sectional study nested within the large Mexican Teacher's Cohort. This study included 491 premenopausal women with a mean age of 42.9 years. Serum 25(OH)D3 levels were measured by liquid chromatography/tandem mass spectrometry. Linear regression and non-linear adjusted models were used to estimate the association of MD with serum 25(OH)D3. Median serum 25(OH)D3 level was 27.3 (23.3–32.8) (ng/ml). Forty one (8%) women had 25(OH)D3 levels in the deficient range (< 20 ng/ml). Body mass index (BMI) and total physical activity were significantly correlated with 25(OH)D3 (r = −0.109, P = 0.019 and r = 0.095, P = 0.003, respectively). In the multivariable linear regression, no significant association was observed between 25(OH)D3 levels and MD overall. However, in stratified analyses, higher serum 25(OH)D3 levels (≥27.3 ng/ml) were significantly inversely associated with percent MD among women with BMI below the median (β = −0.52, P = 0.047). Although no significant association was observed between serum 25(OH)D3 and percent MD in the overall population, specific subgroups of women may benefit from higher serum 25(OH)D3 levels.
    Full-text · Article · Aug 2016
    • "However, on one hand, the antiproliferative effects of Vit D on breast cancer cells also appears to be mediated by the induction of TGF-b (Colston & Hansen, 2002; Koli & Keski-Oja, 1995; Proietti et al., 2011) and by the suppression of the protoncogene c-myc expression (Jensen et al., 2001; Lopes et al., 2012; Saunders et al., 1993). In addition, Vit D can block the proliferative activity of insulin and IGF-1, most likely by increasing the expression of IGFBP-3 and IGFBP-5 (Colston et al., 1998; Lee et al., 2006; Rozen et al., 1997). On the other hand, the promoting effect of Vit D on apoptosis in breast cancer cells appears to be the result of decreased levels of Bcl-2, a redistribution of Bax, a release of cytochrome c, and DNA fragmentation (Nagpal et al., 2005; van den Bemd & Chang, 2002). "
    [Show description] [Hide description] DESCRIPTION: Role of Vitamin D analogues in cancer prevention
    Full-text · Research · Jul 2015 · PLoS ONE
    • "Although our findings were not as strong as those of Brisson, we also found the highest MD in April, and the lowest in December/ January. Vitamin D is known to inhibit the mitogenic effects of IGF-I [45] . Epidemiologic and laboratory findings suggest that the IGF pathway may influence the effect of vitamin D and calcium on breast cancer risk and breast density [17] . "
    [Show abstract] [Hide abstract] ABSTRACT: Background: The role of vitamin D in breast cancer etiology is unclear. There is some, but inconsistent, evidence that vitamin D is associated with both breast cancer risk and mammographic density (MD). We evaluated the associations of MD with month the mammogram was taken, and with vitamin D intake, in a population of women from Norway--a country with limited sunlight exposure for a large part of the year. Methods: 3114 women aged 50-69, who participated in the Norwegian Breast Cancer Screening Program (NBCSP) in 2004 or 2006/07, completed risk factor and food frequency (FFQ) questionnaires. Dietary and total (dietary plus supplements) vitamin D, calcium and energy intakes were estimated by the FFQ. Month when the mammogram was taken was recorded on the mammogram. Percent MD was assessed using a computer assisted method (Madena, University of Southern California) after digitization of the films. Linear regression models were used to investigate percent MD associations with month the mammogram was taken, and vitamin D and calcium intakes, adjusting for age, body mass index (BMI), study year, estrogen and progestin therapy (EPT), education, parity, calcium intakes and energy intakes. Results: There was no statistical significant association between the month the mammogram was taken and percent MD. Overall, there was no association between percent MD and quartiles of total or dietary vitamin D intakes, or of calcium intake. However, analysis restricted to women aged <55 years revealed a suggestive inverse association between total vitamin D intake and percent MD (p for trend = 0.03). Conclusion: Overall, we found no strong evidence that month the mammogram was taken was associated with percent MD. We found no inverse association between vitamin D intake and percent MD overall, but observed a suggestive inverse association between dietary vitamin D and MD for women less than 55 years old.
    Full-text · Article · May 2015
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