Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept study
Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept study
The effect of folic acid (FA) on breast cancer (BC) risk is uncertain. We hypothesised that this uncertainty may be due, in part, to differential effects of FA between BC cells with different phenotypes. To test this we investigated the effect of treatment with FA concentrations within the range of unmetabolised FA reported in humans on the expression of the transcriptome of non-transformed (MCF10A) and cancerous (MCF7 and Hs578T) BC cells. The total number of transcripts altered was MCF10A 75 (70 up-regulated), MCF7 24 (14 up-regulated) and Hs578T 328 (156 up-regulated). Only the cancer-associated gene TAGLN was altered by FA in all three cell lines. In MCF10A and Hs578T cells, FA treatment decreased pathways associated with apoptosis, cell death and senescence, but increased those associated with cell proliferation. The folate transporters SLC19A1, SLC46A1 and FOLR1 were differentially expressed between cell lines tested. However, the level of expression was not altered by FA treatment. These findings suggest that physiological concentrations of FA can induce cell type-specific changes in gene regulation in a manner that is consistent with proliferative phenotype. This has implications for understanding the role of FA in BC risk. In addition, these findings support the suggestion the differences in gene expression induced by FA may involve differential activities of folate transporters. Together these findings indicate the need for further studies of the effect of FA on BC.
folic acid, folate transporters, cell proliferation, breast cancer, microarrays, folate receptors, pathway analysis
1-8
Price, R. Jordan
00d2f9ba-0180-45c3-a655-08ee1b2d18e0
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Price, R. Jordan
00d2f9ba-0180-45c3-a655-08ee1b2d18e0
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Price, R. Jordan, Lillycrop, Karen A. and Burdge, Graham C.
(2016)
Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept study.
Journal of Nutritional Science, 5 (e17), .
(doi:10.1017/jns.2016.8).
Abstract
The effect of folic acid (FA) on breast cancer (BC) risk is uncertain. We hypothesised that this uncertainty may be due, in part, to differential effects of FA between BC cells with different phenotypes. To test this we investigated the effect of treatment with FA concentrations within the range of unmetabolised FA reported in humans on the expression of the transcriptome of non-transformed (MCF10A) and cancerous (MCF7 and Hs578T) BC cells. The total number of transcripts altered was MCF10A 75 (70 up-regulated), MCF7 24 (14 up-regulated) and Hs578T 328 (156 up-regulated). Only the cancer-associated gene TAGLN was altered by FA in all three cell lines. In MCF10A and Hs578T cells, FA treatment decreased pathways associated with apoptosis, cell death and senescence, but increased those associated with cell proliferation. The folate transporters SLC19A1, SLC46A1 and FOLR1 were differentially expressed between cell lines tested. However, the level of expression was not altered by FA treatment. These findings suggest that physiological concentrations of FA can induce cell type-specific changes in gene regulation in a manner that is consistent with proliferative phenotype. This has implications for understanding the role of FA in BC risk. In addition, these findings support the suggestion the differences in gene expression induced by FA may involve differential activities of folate transporters. Together these findings indicate the need for further studies of the effect of FA on BC.
Text
FA-Breast Microarray Paper JNS Revised Unmarked 26 Jan 2016.docx
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Accepted/In Press date: 29 February 2016
e-pub ahead of print date: 26 April 2016
Additional Information:
Funded by World Cancer Research Fund International (2011/42)
Keywords:
folic acid, folate transporters, cell proliferation, breast cancer, microarrays, folate receptors, pathway analysis
Organisations:
Biomedicine, Human Development & Health
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Local EPrints ID: 389798
URI: http://eprints.soton.ac.uk/id/eprint/389798
PURE UUID: 91b7994f-5e4c-4044-b6a7-a78715477ace
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Date deposited: 29 Apr 2016 12:15
Last modified: 15 Mar 2024 02:49
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Author:
R. Jordan Price
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