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...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cambridge University Press
2016-01-01
|
| Series: | Journal of Nutritional Science |
| Subjects: | |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2048679016000082/type/journal_article |
| _version_ | 1811155945365962752 |
|---|---|
| author | R. Jordan Price Karen A. Lillycrop Graham C. Burdge |
| author_facet | R. Jordan Price Karen A. Lillycrop Graham C. Burdge |
| author_sort | R. Jordan Price |
| collection | DOAJ |
| description | 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, seventy-five (seventy up-regulated); MCF7, twenty-four (fourteen 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 that 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. |
| first_indexed | 2024-04-10T04:43:23Z |
| format | Article |
| id | doaj.art-d14f3f0f94b5414d9dea728588bdfe81 |
| institution | Directory Open Access Journal |
| issn | 2048-6790 |
| language | English |
| last_indexed | 2024-04-10T04:43:23Z |
| publishDate | 2016-01-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Nutritional Science |
| spelling | doaj.art-d14f3f0f94b5414d9dea728588bdfe812023-03-09T12:38:49ZengCambridge University PressJournal of Nutritional Science2048-67902016-01-01510.1017/jns.2016.8Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept studyR. Jordan Price0Karen A. Lillycrop1Graham C. Burdge2Academic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UKCentre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, UKAcademic Unit of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UKThe 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, seventy-five (seventy up-regulated); MCF7, twenty-four (fourteen 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 that 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.https://www.cambridge.org/core/product/identifier/S2048679016000082/type/journal_articleFolic acidFolate transportersCell proliferationBreast cancerMicroarraysFolate receptorsPathway analysis |
| spellingShingle | R. Jordan Price Karen A. Lillycrop Graham C. Burdge Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept study Journal of Nutritional Science Folic acid Folate transporters Cell proliferation Breast cancer Microarrays Folate receptors Pathway analysis |
| title | Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept study |
| title_full | Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept study |
| title_fullStr | Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept study |
| title_full_unstemmed | Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept study |
| title_short | Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept study |
| title_sort | folic acid induces cell type specific changes in the transcriptome of breast cancer cell lines a proof of concept study |
| topic | Folic acid Folate transporters Cell proliferation Breast cancer Microarrays Folate receptors Pathway analysis |
| url | https://www.cambridge.org/core/product/identifier/S2048679016000082/type/journal_article |
| work_keys_str_mv | AT rjordanprice folicacidinducescelltypespecificchangesinthetranscriptomeofbreastcancercelllinesaproofofconceptstudy AT karenalillycrop folicacidinducescelltypespecificchangesinthetranscriptomeofbreastcancercelllinesaproofofconceptstudy AT grahamcburdge folicacidinducescelltypespecificchangesinthetranscriptomeofbreastcancercelllinesaproofofconceptstudy |