Low expression of reduced folate carrier-1 and folylpolyglutamate synthase correlates with lack of a deleted in colorectal carcinoma mRNA splice variant in normal-appearing mucosa of colorectal carcinoma patients
Artikel i vetenskaplig tidskrift, 2005

BACKGROUND: Cellular folate deficiency leads to DNA strand breaks, mutations, and aberrant methylation and might be a risk factor for colorectal cancer (CRC). The putative tumor suppressor gene deleted in colorectal carcinoma (DCC) is one of several genes the expression of which seems to be affected by the folate concentration at the tissue level. Decreased expression of DCC may be caused by LOH or hypermethylation, i.e. by events that might be linked to folate deficiency. The purpose of this study was to analyze if the folate level and the gene expression levels of reduced folate carrier (RFC-1) and folylpolyglutamate synthase (FPGS) had impact on the expression of DCC splice variants. METHODS: Quantification of RFC-1 and FPGS expression in mucosa of 53 CRC patients was performed using real-time PCR whereas DCC splicing variants were detected by automated capillary gel electrophoresis. Total reduced folate concentration was measured with the FdUMP-binding assay (n = 22). RESULTS: Significantly higher expression levels of RFC-1 (p = 0.026) and FPGS (p = 0.05) were found in mucosa expressing the splice variant DCC342 compared to mucosa that did not. Furthermore, multivariate analysis showed that RFC-1 and FPGS (r = 0.49, p = 0.01) as well as folate and RFC-1 (r = 0.56, p = 0.023) were correlated only in mucosa expressing DCC342. CONCLUSIONS: In conclusion, the present study points to a potential influence of folates in regulating DCC expression at multiple levels involving post-transcriptional pathways. The results may provide a basis for a detailed investigation of molecular mechanisms involved in folate regulation of DCC expression.

Neoplasm/*genetics

RNA

Molecular Sequence Data

Middle Aged

Intestinal Mucosa/*chemistry

Multivariate Analysis

Aged

Male

Female

Colorectal Neoplasms/chemistry/*genetics/pathology

Sweden

Amino Acid Sequence

Genes

Aged

Peptide Synthases/analysis/*genetics

Neoplastic

Reverse Transcriptase Polymerase Chain Reaction

Gene Expression Regulation

Adenocarcinoma/chemistry/*genetics/pathology

80 and over

*Alternative Splicing

Adult

Membrane Transport Proteins/analysis/*genetics

DCC/genetics

Humans

Folic Acid Deficiency/genetics

Författare

Yvonne Wettergren

Elisabeth Odin

Göteborgs universitet

Staffan Nilsson

Göteborgs universitet

Chalmers, Matematiska vetenskaper, matematisk statistik

Roger Willen

Göran Carlsson

Bengt Gustavsson

Göteborgs universitet

Cancer Detection and Prevention

0361-090X (ISSN) 1525-1500 (eISSN)

Vol. 29 4 348-55

Ämneskategorier

Kirurgi

DOI

10.1016/j.cdp.2005.06.006

PubMed

16122883