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DNA methylation and expression of the folate transporter genes in colorectal cancer
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
2015 (English)In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 36, no 7, 5581-5590 p.Article in journal (Refereed) Published
Abstract [en]

Folate has a central role in the cell metabolism. This study aims to explore the DNA methylation pattern of the folate transporter genes FOLR1, PCFT, and RFC1 as well as the corresponding protein expressions in colorectal cancer (CRC) tissue and adjacent non-cancerous mucosa (ANCM). Our results showed statistically significant differences in the DNA-methylated fraction of all three genes at several gene regions; we identified three differentially methylated CpG sites in the FOLR1 gene, five CpG sites in the PCFT gene, and six CpG sites in the RFC1 gene. There was a pronounced expression of the FR alpha and RFC proteins in both the CRC and ANCM tissues, though the expression was attenuated in cancer compared to the paired ANCM tissues. The PCFT protein was undetectable or expressed at a very low level in both tissue types. Higher methylated fractions of the CpG sites 3-5 in the RFC1 gene were associated with a lower protein expression, suggestive of epigenetic regulation by DNA methylation of the RFC1 gene in the colorectal cancer. Our results did not show any association between the RFC and FR alpha protein expression and tumor stage, TNM classification, or tumor location. In conclusion, this is the first study to simultaneously evaluate both DNA methylation and protein expression of all three folate transporter genes, FOLR1, PCFT, and RFC1, in colorectal cancer. The results encourage further investigation into the possible prognostic implications of folate transporter expression and DNA methylation.

Place, publisher, year, edition, pages
2015. Vol. 36, no 7, 5581-5590 p.
Keyword [en]
CpG, T-DMR, Reduced folate carrier, CRC, Immunohistochemistry
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:oru:diva-45755DOI: 10.1007/s13277-015-3228-2ISI: 000359569000086PubMedID: 25697897Scopus ID: 2-s2.0-84938198358OAI: oai:DiVA.org:oru-45755DiVA: diva2:852436
Note

Funding Agencies:

Lions Cancer Foundation, Nyckelfonden

Research committee of Örebro county council

Available from: 2015-09-09 Created: 2015-09-09 Last updated: 2015-09-09Bibliographically approved

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