| 1. |
- Odin, Elisabeth, 1955, et al.
(författare)
-
Altered gene expression of folate enzymes in adjacent mucosa is associated with outcome of colorectal cancer patients.
- 2003
-
Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 9:16 Pt 1, s. 6012-9
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of this study was to analyze whether gene expression levels of folate enzymes in adjacent mucosa were associated with outcome of colorectal cancer patients. EXPERIMENTAL DESIGN: Real-time PCR was used to quantify expression levels of folate-associated genes including the reduced folate carrier (RFC-1), folylpolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH),and thymidylate synthase (TS) in tumor tissue and adjacent mucosa of patients with primary colorectal cancer (n=102). Furthermore, reduced folates in the tissues were measured with a binding-assay method. RESULTS: Mean gene expression levels of RFC-1, FPGS, GGH, and TS were significantly higher in tumor biopsies compared with mucosa. Univariate and multivariate analyses showed that the FPGS gene expression level in mucosa, but not in tumor, was a prognostic parameter independent of the clinicopathological factors with regard to survival. Patients with high FPGS levels (>0.92) in mucosa also showed significantly higher total folate concentrations (P=0.03) and gene expression levels of RFC-1 (P<0.01), GGH (P<0.01), and TS (P=0.04) compared with patients with low FPGS levels. The total reduced folate concentration correlated with the gene expression levels of RFC-1 and FPGS but not with TS or GGH. CONCLUSION: Our results suggest that normal-appearing colonic mucosa adjacent to primary colon cancer can show altered gene expression levels of FPGS that may have bearing on the development of aggressive metastatic behavior of the tumor and on tumor-specific survival.
|
|
| 2. |
- Wettergren, Yvonne, 1957, et al.
(författare)
-
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
- 2005
-
Ingår i: Cancer Detect Prev. - : Elsevier BV. - 0361-090X .- 1525-1500. ; 29:4, s. 348-55
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
