Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Gene/Protein
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Target Concepts:
Gene/Protein
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Query: EC:1.5.1.3 (
dihydrofolate reductase
)
5,819
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A cDNA library has been constructed from the poly(A)+ mRNA of oestrogen-stimulated ZR-75-1 human breast cancer cells. Screening by differential hybridization has identified eight clones which are stimulated between 4- and 16-fold by oestrogen. Two clones (pLIV-1) that are stimulated 4-fold, hybridize to three different mRNA species. A further five recombinants encode for a mRNA 600 bp long which is induced greater than 16-fold and have been shown to cross-hybridize to the oestrogen-responsive clone, pS2, isolated from the MCF-7 breast cancer cell line.
Oestradiol
was shown to be without detectable effect upon the expression of mRNA for
dihydrofolate reductase
, which is reported to be oestrogen regulated in MCF-7 cells. Actin gene expression is also unresponsive to oestradiol in ZR-75-1 cells. These results suggest that pLIV-1 represents a previously unidentified mRNA that may be involved in the oestrogen-regulated growth of ZR-75-1 human breast cancer cells.
...
PMID:Effects of oestrogen on the expression of a 4.4 kb mRNA in the ZR-75-1 human breast cancer cell line. 290 3
We have studied the effects of estrogen and the antiestrogen tamoxifen on the regulation of
dihydrofolate reductase
(
DHFR
) gene expression in a methotrexate-resistant (MTXR) human breast cancer cell line MCF-7, which contains a 50-fold increase in the level of
DHFR
enzyme and amplified
DHFR
gene sequences. Despite their selection for methotrexate resistance, the MTXR cells have retained many characteristics of the parental MCF-7 cell line. Concentrations of estrogen receptors as well as their binding affinity to estradiol are identical in both cell lines. MTXR MCF-7 cells remain sensitive to estrogen and respond to estradiol with an induction of progesterone receptors, as well as increases in the rate of DNA synthesis and cell growth. Incubation of MTXR MCF-7 cells with estradiol results in an additional 1.5- to 3.0-fold increase in their already elevated level of
DHFR
. The hormone-induced increases in DNA synthesis and
DHFR
levels are similar both with respect to the time course of inductions, as well as their dose response to estradiol. However, these two estrogen-induced effects are not coupled, since the induction of
DHFR
occurs even in the absence of concomitant DNA synthesis.
Estradiol
has no effect on
DHFR
enzyme stability; thus, the entire effect of estrogen on
DHFR
levels results from the increased synthesis of this housekeeping enzyme. In contrast, treatment of MTXR MCF-7 cells with the antiestrogen tamoxifen reduces the rate of
DHFR
enzyme synthesis, resulting in lower cellular levels of
DHFR
. These MTXR MCF-7 cells represent a useful model in which to study the mechanisms involved in the modulation of
DHFR
gene expression by estrogen and tamoxifen. Since the level of
DHFR
is a critical determinant of methotrexate cytotoxicity understanding, the regulation of
DHFR
gene expression may have clinical implications for the use of hormonal therapy in combination with chemotherapy for the treatment of breast cancer.
...
PMID:Effects of estrogen and tamoxifen on the regulation of dihydrofolate reductase gene expression in a human breast cancer cell line. 397 32
