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
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Journal of Molecular Endocrinology (1998) 20, 157–162
    • "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 · Journal of Cell Communication and Signaling
    • "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
    • "IGFBP-3 is the main IGFBP found in human serum and has the potential to either inhibit or enhance IGF actions in many cell types: IGFBP-3 can restrict tumour growth and progression by limiting IGF-mitogenic and cell survival actions. The actions of many anti-proliferative agents appear to operate, at least in part, via upregulation of endogenous IGFBP-3 produced by the tumour cells including the tumour suppressor gene, p53 (Buckbinder et al. 1995 ), transforming growth factorbeta (TGF-beta) (McCaig et al. 2002a), retinoids (Gucev et al. 1996), vitamin D (Colston et al. 1998), the anti-estrogen, Tamoxifen (Huynh and Pollak 1994) and the fatty acid, butyrate (Collard et al. 2003). Accumulating evidence indicates that most of the IGFBPs can also act in an intrinsic manner, independent of IGF-binding , affecting various aspects of cell function in both a positive and negative manner. "
    [Show abstract] [Hide abstract] ABSTRACT: Epigenetics refers to heritable changes in gene expression that are independent of alterations in DNA sequence. It is now accepted that disruption of epigenetic mechanisms plays a key role in the pathogenesis of cancer: culminating in altered gene function and malignant cellular transformation. DNA methylation and histone modifications are the most widely studied changes but non-coding RNAs such as miRNAs are also considered part of the epigenetic machinery. The insulin-like growth factor (IGF) axis is composed of two ligands, IGF-I and -II, their receptors and six high affinity IGF binding proteins (IGFBPs). The IGF axis plays a key role in cancer development and progression. As IGFBP genes have consistently been identified among the most common to be aberrantly altered in tumours, this review will focus on epigenetic regulation of IGFBP-3 in cancer for which the majority of evidence has been obtained.
    Full-text · Article · Apr 2015
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