Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the serum activity of the fifth fraction of L-lactate: NAD-oxidoreductase (E.C.1.1.1.27) and serum alkaline phosphatase activity prior to diagnostic curettage in patients with abnormal and atypical endomertial hyperplasia. We also determined them in 75 patients with carcinoma of the endometrium, 80 patients with glandular cystic endometrial hyperplasia and a "normal" control group of 70 patients. In the statistical evaluation we found a significantly high incidence of low AP activity and elevated LDH5 in the group of patients with glandular cystic endometrial hyperplasia, as well as in patients with precancerous lesions of the endometrium and carcinoma of the endometrium. The findings raise the question of whether these changes in the serum activity of the given enzymes are only a response to a given hormonal modulation.
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PMID:Alkaline phosphatase activity in relation to LDH5 (L-lactate: NAD+ - oxidoreductase, E.C.1.1.1.27) in patients with precancerous conditions of the endometrium. 61 58

This paper summarizes our most recent results of steroid enzyme studies on cultured breast and endometrial cancer cells. It deals mainly with estrogen 17 beta-hydroxysteroid oxidoreductase (17 beta HSOR) activity, which presides over estradiol (E2) and estrone (E1) interconversion, a major metabolic pathway of estrogens. Assessment of either the oxidative or reductive component of 17 beta HSOR was carried out on intact cells by means of an original approach based on reverse phase-high performance liquid chromatography and radioactive detection on line. This system allows the continuous monitoring of both precursor degradation and formation of several radiometabolites to assess rates and direction of steroid metabolism. Overall, hormone-responsive, estrogen receptor (ER)-positive cells, regardless of whether they were derived from breast (MCF7) or endometrial (Ishikawa) tumor tissues, showed a prevalence for reductive metabolism (E1-->E2), whilst oxidative pathways (E2-->E1) were largely dominant in non-responsive, ER-poor mammary (MDA-MB231) and endometrial (HEC-1A) cells. The above estimates of 17 beta HSOR activity were at variance with those obtained using the classical enzymology approach, not only in quantitative terms (being markedly lower using intact cell analysis), but also because the prevalent direction of estrogen metabolism was often reversed. Although striking methodological differences may well account for this discrepancy, intact cell analysis is undoubtedly more similar to the in vivo state than the artificial requirements of classical enzymology procedures.
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PMID:17 beta-hydroxysteroid oxidoreductase activity in intact cells significantly differs from classical enzymology analysis. 894 90

We have previously reported that antiestrogens stimulate quinone reductase (NAD(P)H:(quinone-acceptor) oxidoreductase (QR or NQO1); EC 1.6.99.2) enzymatic activity, an action that may provide protective effects against the toxicity and mutagenicity caused by quinones. We have now investigated the transcriptional regulation of the QR gene by antiestrogens. In transfection experiments employing the 5'-flanking (863-base pair) region of the human QR gene promoter with its electrophile/antioxidant response element (EpRE/ARE) or deleted or mutated constructs, we observe that antiestrogens induced an increase in QR gene promoter reporter activity in estrogen receptor (ER) negative breast cancer and endometrial cancer cells transfected with ER, and this induction by antiestrogens was repressed by estradiol. The stimulation of QR transcriptional activity required the 31-base pair electrophile-responsive region from the human QR gene promoter and a functional ER. Intriguingly, antiestrogens were stronger activators of the QR EpRE via the ER subtype ERbeta than ERalpha. Oligonucleotide gel mobility and antibody shift assays reveal that the ER binds to the EpRE but is only a minor component of the proteins bound to the EpRE in ER-containing MCF-7 breast cancer cells. While binding of ERbeta to the estrogen response element was weaker when compared with ERalpha, ERbeta and ERalpha showed similar binding to the EpRE. Together these findings provide evidence that QR gene regulation by the antiestrogen-occupied ER is mediated by the EpRE-containing region of the human QR gene and indicate that the ER is one of the complex of proteins that binds to the EpRE. In addition, that ERbeta is a more potent activator at EpRE elements than is ERalpha suggests that the different levels of these two receptors in various estrogen target cells could impact importantly on the antioxidant potency of antiestrogens in different target cells. These findings have broad implications regarding the potential beneficial effects of antiestrogens since EpREs mediate the transcriptional induction of numerous genes, including QR, which encode chemoprotective detoxification enzymes.
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PMID:Transcriptional regulation of the human quinone reductase gene by antiestrogen-liganded estrogen receptor-alpha and estrogen receptor-beta. 973 13