Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.5.7.1 (
methylenetetrahydrofolate reductase
)
2,116
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The present study aimed to investigate the effect of knocking-down
methylenetetrahydrofolate reductase
(
MTHFR
) on the survival of the human gastric cancer cell line MKN45. Antisense and small interfering RNA (siRNA) plasmids were used to target
MTHFR
in MKN45. Meanwhile, we also constructed a wild-type
MTHFR
plasmid to assess the effect of over-expression of this protein on cell viability. The knock-down of
MTHFR
decreased cell survival by approximately 30% compared to the control and resulted in cell cycle arrest at the G2 phase. These cells also had lower levels of
c-myc
compared to control cells, while over-expression of
MTHFR
increased cell proliferation and induced the down-regulation of p21WAF1 and hMLH1. Inhibiting
MTHFR
with either antisense or siRNA decreases the viability of methionine-dependent transformed gastric cancer cells and suggests that
MTHFR
inhibition may be a novel anticancer approach.
...
PMID:Knock-down of methylenetetrahydrofolate reductase reduces gastric cancer cell survival: an in vitro study. 1848 1
There is limited available information on the effects of arsenic on enzymes participating in the folate cycle. Therefore, our aim was to evaluate the effects of sodium arsenite on the protein levels of
methylenetetrahydrofolate reductase
(
MTHFR
) and dihydrofolate reductase (DHFR) and its further relationship with the expression MT1/2 and
c-myc
in MCF-7 cells. Arsenite treatment (0-10 microM) for 4 h decreased
MTHFR
levels in a concentration-dependent fashion without significant effects on DHFR. The effects on
MTHFR
were observed at arsenite concentrations not significantly affecting cell viability. We also observed an increase in S-phase recruitment at all concentrations probed. Lower concentrations (<5 microM) induced cell proliferation, showing a high proportion of BrdU-stained cells, indicating a higher DNA synthesis rate. However, higher concentrations (> or =5 microM) or longer treatment periods induced apoptosis. Arsenite also induced dose-dependent increases in MT1/2 and c-Myc protein levels. The levels of
MTHFR
were inversely correlated to MT1/2 and c-Myc overexpression and increased S-phase recruitment. Our findings indicate that breast epithelial cells are responsive to arsenite and suggest that exposure may pose a risk for breast cancer. The reductions in
MTHFR
protein levels contribute to understand the mechanisms underlying the induction of genes influencing growth regulation, such as
c-myc
and MT1/2. However, further research is needed to ascertain if the effects here reported following short-time and high-dose exposure are relevant for human populations chronically exposed to low arsenic concentrations.
...
PMID:Sodium arsenite alters cell cycle and MTHFR, MT1/2, and c-Myc protein levels in MCF-7 cells. 1976 32
