The Expression of Riboflavin Transporters in Human Colorectal Cancer

Anticancer Res. 2018 May;38(5):2659-2667. doi: 10.21873/anticanres.12508.

Abstract

Background/aim: Riboflavin transport in enterocytes is mediated by three translocators: RFVT3 located on the apical membrane, and RFVT1 and RFVT2 on the basolateral membrane. The aim of this study was to investigate whether the expression levels of RFVTs are altered in human colorectal cancer (CRC).

Materials and methods: In human colon adenocarcinoma cell lines (CaCo2, DLD-1, HT-29) and in tissues of patients with CRC, gene and protein expression levels were evaluated by real time-polymerase chain reaction and western blotting. Intracellular flavin content was determined by high-performance liquid chromatography.

Results: RFVT3 and RFVT2 gene and protein expression levels were higher in DLD-1 and HT-29 compared to Caco2 cells. In HT-29 cells, the RFVT1 protein level was drastically lower. These differences are presumably responsible for the higher total flavin content in DLD-1 and HT-29 cells. In tumor tissues of patients with CRC, RFVT1 content was reduced at both protein and mRNA levels compared to normal mucosa. RFVT3 and RFVT2 gene expression levels were increased, while protein expression was reduced, with a small reduction in riboflavin amount.

Conclusion: This study provides first evidence that transcription/translation of RFVTs are profoundly altered in CRC.

Keywords: Colorectal cancer; cell lines; flavin cofactor homeostasis; riboflavin; riboflavin transporters.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Aged
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Enterocytes / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intestinal Mucosa / metabolism
  • Male
  • Membrane Transport Proteins / biosynthesis*
  • Membrane Transport Proteins / genetics
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • Riboflavin / metabolism*

Substances

  • Membrane Transport Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Riboflavin