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

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Query: EC:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In situ methodologies allow qualitative and semi-quantitative analysis of spatial gene expression in whole organisms or tissues. We have applied quantitative autoradiography to in situ hybridizations of sections from human breast tumor xenografts to measure mRNA levels for ornithine decarboxylase, estrogen receptor, transforming growth factor alpha, and glyceraldehyde-3-phosphate dehydrogenase. Comparisons of control and tamoxifen-treated animals show significant decreases in MCF-7 tumor estrogen receptor mRNA levels in the drug-treated animals. Combining quantitative autoradiography with in situ hybridization allows measurement of absolute rather than relative mRNA levels for genes of interest, and to monitor effector-induced changes in these mRNAs in vivo.
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PMID:Measurement of mRNA levels in tumor xenografts with quantitative autoradiography and in situ hybridization. 778 31

Sex hormones influence neurite outgrowth and synaptogenesis in certain hormone-dependent areas of the rat brain during neonatal development. These alterations are thought to mediate changes in brain structure and function between the sexes. Growth-associated protein 43 kDa (GAP-43) gene expression is estrogen-regulated in the adult ventromedial hypothalamus (VMH) and sexually dimorphic (M:F = 1.8:1) in adult cortex (CTX). Such effects intimate hormonal regulation of synaptic plasticity. To investigate the nature of these dimorphisms, the present study examined the ontogeny of expression of mRNAs encoding 3 neural-specific proteins: GAP-43, SCG10, and synaptosomal-associated protein 25 kDa (SNAP-25); and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in the VMH and CTX; and also the effects of altering the neonatal sex hormonal milieu on the development of these adult dimorphisms. Levels of specific mRNAs in VMH and CTX were quantitated by slot-blot hybridization in rats of both sexes at different postnatal ages. To determine the involvement of neonatal sex hormones on the levels of these mRNAs, male neonatal rat pups were treated with an estrogen receptor antagonist or an aromatase inhibitor, and neonatal female pups were treated with testosterone or estrogen prior to slot-blot evaluations in adulthood. In VMH, GAP-43 mRNA levels were high on days P1 and P4 with a 3-fold decrease by day P23; in CTX, GAP-43 mRNA first increased by day P11, then fell to baseline by day P23. In VMH, SCG10 mRNA showed only small increases with time; but in CTX, there was a 5-fold drop from days P4 to P23. In VMH, SNAP-25 mRNA was low and changed only slightly; but in CTX there was a 5-fold increase between days P4 and P60. At birth, there was no sex dimorphism in either VMH or CTX, but the levels of all 3 neural-specific mRNAs were sexually dimorphic in adult CTX (M:F = 1.76 for GAP-43, 1.46 for SCG10, 1.44 for SNAP-25). GAPDH mRNA levels were regulated developmentally in VMH and CTX, but there was no sex dimorphism in either area. In male rats who received either an estrogen antagonist or aromatase inhibitor at birth, the CTX GAP-43 and SNAP-25 mRNA levels fell by 30%, to levels similar to untreated females. Conversely, in female rats, neonatal treatment with either testosterone or estrogen increased GAP-43 and SNAP-25 mRNA levels by about 30%, to levels similar to the untreated adult male. SCG10 levels did not demonstrate neonatal hormonal dependence.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ontogeny, sex dimorphism, and neonatal sex hormone determination of synapse-associated messenger RNAs in rat brain. 825 71

In MCF7 human breast cancer cells, the antiestrogens 4-hydroxy-tamoxifen and ICI 164,384 inhibit the mitogenic activity of epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I). These growth factors also stimulate the expression of cathepsin-D and pS2 genes. Therefore, we studied the effects of antiestrogens on growth factor induction of pS2 and cathepsin-D mRNA. The two antiestrogens strongly inhibited the transcriptional induction of pS2 by growth factors. On the contrary, estradiol and IGF-I or EGF had an additive effect on pS2 mRNA accumulation. Growth factor induction of cathepsin-D was also inhibited by ICI 164,384. By contrast, 4-hydroxytamoxifen had an agonist effect on cathepsin-D and an additive effect on IGF-I-induced mRNA. When 12-O-tetradecanoylphorbol-13-acetate or 8-bromo-cAMP (8-Br-cAMP) was used instead of growth factors, similar effects of 4-hydroxytamoxifen and ICI 164,384 were obtained on pS2 (12-O-tetradecanoylphorbol-13-acetate and 8-Br-cAMP) and cathepsin-D (8-Br-cAMP) induction. A mechanism based on the classical competitive inhibition by antiestrogens of estrogen binding and action on the estrogen receptor was very unlikely, as 1) no antigrowth factor activity was obtained with R5020, which was a potent inhibitor of estrogen induction of pS2 and cathepsin-D mRNA; 2) in the Ishikawa endometrial cancer cell line, the cathepsin-D gene is unresponsive to estrogen, but was inhibited by antiestrogen after its induction by EGF or 8-Br-cAMP; and 3) the residual estrogen concentration in cells was too low to induce the expression of estrogen-specific genes. However, antiestrogens did not inhibit the expression of all genes induced by growth factors, as they were without effect on IGF-I induction of glyceraldehyde-3-phosphate dehydrogenase mRNA. These results demonstrate that antiestrogens can modulate the transcription of some growth factor-induced genes and strongly suggest that this effect is not due to interference with residual estrogens.
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PMID:Synthetic antiestrogens modulate induction of pS2 and cathepsin-D messenger ribonucleic acid by growth factors and adenosine 3',5'-monophosphate in MCF7 cells. 834 99

The goal of this study was to determine which of the 10 functional metallothionein (MT) genes are expressed in four human breast cancer cell lines and whether expression varies among the cell lines. Using reverse transcription polymerase chain reaction (RT-PCR) technology, it was shown that there was no expression of mRNA for the MT-1A, MT-1B, MT-1F, MT-1G, MT-1H, MT-3, and MT-4 genes in any of the four cell lines. All four cell lines were shown to express mRNA for the MT-2A and MT-1X genes. The expression level of mRNA for the MT-2A gene demonstrated modest differences among the cell lines, whereas expression of the MT-1X gene was consistent. In contrast, mRNA for the MT-1E gene was expressed in only two of the four cell lines and expression correlated to the estrogen receptor status of the cell lines. The two estrogen-receptor-positive cell lines showed no mRNA expression for the MT-1E gene. In the two estrogen-receptor-negative cell lines, mRNA expression for the MT-1E gene was elevated with expression levels similar to the housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase. The cellular content of MT protein was also shown to be elevated in the estrogen-receptor-negative cell lines that express MT-1E mRNA. These results suggest a possible relationship between estrogen receptor status and MT-1E gene expression in human breast cancer.
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PMID:Differential expression of the MT-1E gene in estrogen-receptor-positive and -negative human breast cancer cell lines. 942 19

Several clinical studies have suggested that the content of estrogen receptor (ER) in breast tumors influences the survival, tumor recurrence, and response to antiestrogen therapies. Therefore, the ability to precisely quantitate the ER content in tumor tissues will be of significant benefit to women with breast cancer. Although immunohistochemical and polymerase chain reaction (PCR) methods have been described for the detection and semiquantitation of ER, none of them precisely quantitate ER copy numbers in tumor samples. In the present report we describe a molecular approach to accurately quantitate ER mRNA copy numbers using a reverse-transcription PCR (RT-PCR) template competition method. A competitor template was devised by inserting unrelated nucleic acid sequences into an ER cDNA clone. A template competitive RT-PCR analysis was then performed to determine the number of copies of ER mRNA. As a standard of reference for the ER mRNA copy numbers from various samples, the mRNA copy numbers of a constitutively expressed gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), were also quantitated. The ER quantitations were performed in three positive cell lines, MCF-7, T47D, and ZR-75, and two positive tumor tissues by this approach. Our results described here show that among the cell lines studied, T47D expresses the highest copy numbers of ER. We also present here that ER as low as 10(3) copies per 10(5) copies of GAPDH can be detected and quantitated in tumor samples by the template competition method. In addition, the molecular approach can simultaneously detect, distinguish, and quantitate exon deletion variant copy numbers of ER. The results described in this report indicate that the ratios of exon 7 deletion variant to wild type in the tumor tissues are significantly higher than in the cell lines studied.
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PMID:Quantitation of estrogen receptor mRNA copy numbers in breast cancer cell lines and tumors. 957 Aug 31

Objectives were to establish conditions for preparation, growth, and maintenance of a primary culture cell model of fetal uterine cells, and to determine whether cells maintained under those conditions would maintain their capacity to respond to estrogen stimulation in vitro. Fetal uteri (n = 19) were enzymatically dispersed and grown on Type 1 collagen in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum. Fetal-uterine cells appeared fibroblast-like and exhibited positive immunostaining for both vimentin and cytokeratin. Effects of gestational age (GA), passage number (p), and hormonal treatment on appearance of specific mRNAs were determined by RT-PCR; relative concentrations of products determined by densitometry were analyzed as the ratio of target cDNA to the GAPDH loading control. Cells expressed mRNAs for estrogen receptor (ER), TGF-beta, EGF-R, PRL-R, IL-1 alpha, and IL-6. ER mRNA was greater at 185-200 than at 100-110 d GA (P < 0.01). All specific mRNAs examined were greater in p5 cells than p2 at both 100-110 (P < 0.01) and 185-200 d GA (P < 0.02). There was no effect of estradiol on these specific mRNAs in cells from 100-110 d GA; at 185-200 d GA, there was an estradiol (1.0 nM) effect both at 6 hr (P < 0.001) and 24 hr (P < 0.02). Overall, there was an effect of 8-br-cAMP (1 mM; 6 h) on specific mRNAs in cells at both 100-110 (P < 0.001) and 185-200 d GA (P < 0.001). In p5 cells from Day 185-200 GA, there was increased cell proliferation (P < 0.001) in response to estradiol (1 nM; 24 hr). These data suggest that primary fetal uterine cells retain their age-specific and hormone-responsive phenotype under these in vitro conditions.
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PMID:Expression of estrogen receptor and maintenance of hormone-responsive phenotype in bovine fetal uterine cells. 960 96

During the preovulatory period, estrogen up-regulates estrogen receptor-alpha (ER) gene expression in endometrium in female mammals of all species examined. The purpose of this study was to determine directly whether estradiol up-regulates ER mRNA by increasing the stability of the message. Endometrial tissue was collected from ovariectomized ewes 18 h after the ewes were injected with 50 microg estradiol. Previous work indicated rapid accumulation of ER mRNA at this time. Estradiol increased uterine weights (to 157 +/- 15%) as well as steady-state concentrations of ER (to 309 +/- 37%), progesterone receptor (PR; to 165 +/- 19%), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH; to 374 +/- 32%) mRNAs in endometrium, compared to control levels of 100%. The effects of estradiol on ER mRNA stability in endometrium were measured in explants cultured with the transcription inhibitor 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole, as well as by labeling RNA in vivo with 4-thiouridine. Both assays indicated that estradiol enhanced ER mRNA stability (half-life increased from 9 h to >/= 24 h). The estradiol effect was specific, because the stabilities of PR, GAPDH, and c-fos mRNAs were unaffected by treatment. Thus, estradiol up-regulates steady-state concentrations of ER mRNA in endometrium by a novel posttranscriptional mechanism.
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PMID:Estradiol up-regulates estrogen receptor-alpha messenger ribonucleic acid in sheep endometrium by increasing its stability. 985 97

Two estrogen receptor (ER) isoforms, ERalpha and ERbeta, have been described. However, no information is available in any species regarding the comparison of ERalpha and ERbeta levels in pregnant intrauterine tissues. We investigated 1) distribution of ERalpha and ERbeta mRNA in myometrium, amnion, choriodecidua, and placenta; 2) their abundance in intrauterine tissues at term not in labor (NIL) and in spontaneous term labor (STL); and 3) immunolocalization of ERalpha and ERbeta in pregnant rhesus monkey myometrium. Myometrium, amnion, choriodecidua, and placenta were obtained at cesarean section from monkeys in STL at 156-166 days gestational age (GA) (n = 4) and from control monkeys NIL at 140-152 days GA (n = 4). RT-PCR was conducted to determine ERalpha and ERbeta and glyceraldehyde-3-phosphate dehydrogenase mRNA abundance in four intrauterine tissues of the pregnant rhesus monkey. The cloned ERbeta PCR fragment was subjected to sequence analysis. ERalpha and ERbeta were localized in the myometrium by immunohistochemistry. We demonstrated that 1) rhesus monkey ERbeta shares >97% identity with human ERbeta in the region sequenced; 2) both ERs were expressed in myometrium, amnion, and choriodecidua but not in placenta in the current study; 3) ERalpha and ERbeta were differentially distributed in myometrium and amnion; 4) ERalpha and ERbeta were immunolocalized in myometrial smooth cells and smooth muscle and endothelial cells of the myometrial blood vessels. The biological significance of these quantitative differences in ER subtypes merits further study.
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PMID:Differential distribution of ERalpha and ERbeta mRNA in intrauterine tissues of the pregnant rhesus monkey. 1064 27

Colon cancer incidence and mortality rates are lower in females compared with males, and numerous epidemiological studies suggest that estrogen replacement therapy (ERT) reduces cancer risk in postmenopausal women. Two estrogen receptor (ER) subtypes, ERalpha and ERbeta, mediate genomic effects in target cells. The aim of this study was to determine the relative mRNA expression levels for ER subtypes and ERbeta isoforms in colon tumors, normal colonic mucosa, and colon cancer cell lines. ERalpha and ERbeta isoform mRNA levels were investigated in paired samples of colon tumors and normal mucosa from 26 patients using comparative reverse transcription-PCR and then Southern analyses. Constitutive steroid hormone receptor mRNA levels were determined for five colon adenocarcinoma cell lines using reverse transcription-PCR, and ERbeta levels were further studied in Caco-2 cells using Northern and Western analyses. ERbeta mRNA steady-state levels (relative to glyceraldehyde-3-phosphate dehydrogenase mRNA) were significantly decreased in colon tumors compared with normal mucosa in female patients. ERbeta1 and ERbeta2 isoform mRNA levels were significantly decreased in tumors from female patients, and ERbeta1 mRNA levels were also significantly lower in tumors from female patients compared with tumors from males. ERalpha mRNA levels were much lower than ERbeta levels and were similar between normal mucosa and tumor samples in both genders. ERbeta mRNA was detected in Caco-2, T84, and SW1116 cell lines and all lines were essentially negative for ERalpha mRNA. Caco-2 cells coexpressed ERbeta1, ERbeta2, and ERbeta5 mRNA, though a single protein transcript was observed. ERbeta protein was detected in normal colonic superficial epithelium, vascular smooth muscle and endothelium, and enteric neurons by immunohistochemistry. These data show that ERbeta is the predominant ER subtype in the human colon and that decreased levels of ERbeta1 and ERbeta2 mRNA are associated with colonic tumorigenesis in females. This information suggests that activation of ERbeta-mediated processes in the superficial colonic epithelium may have a role in the preventive effects observed for female gender and ERT usage.
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PMID:Expression of estrogen receptor (ER) subtypes and ERbeta isoforms in colon cancer. 1121 61

We will describe the identity and function of two unexpected estrogen binding proteins from rat brain cell membranes in search for the putative membrane estrogen receptor (mER). An E-6-BSA column retained a distinctive 37-kDa protein that showed 100% homology with glyceraldehyde-3-phosphate dehydrogenase (GAPDH). A P-3-BSA column also retained the same protein but with less affinity. E-6-BSA bound to GAPDH with an IC50 of 50 nM, whereas the IC50 for P-3-BSA was about 500 nM. A dose of 10 nM 17beta-estradiol stimulated the catalysis of GAPDH, whereas progesterone at 100 nM inhibited it. Other steroids were ineffective. We examined if GAPDH activity would change during the rat estrous cycle, and what would be the effect of ovariectomy and estrogen treatment. The hippocampus and cerebellum were collected and GAPDH catalysis in both cytosolic and plasmalemmal-microsomal fractions was tested. The highest activity was found in Proestrus morning and the lowest in Estrus in both fractions. After ovariectomy (3 weeks) the hippocampus membrane fraction showed significantly reduced activity compared to that of Diestrus. An injection of estradiol in ovariectomized rats (10 microg/rat, s.c.) increased GAPDH activity in the hippocampus membrane fractions close to 60% from that of ovariectomized oil-treated controls 24 h after treatment maintaining similar levels by 48 h. No changes were detected in the preparations from the cerebellum of the same rats. The other protein retained by E-BSA columns was a 55-kDa protein identified as beta-tubulin. Two other proteins were also co-purified from the rat hippocampus: a 37-kDa (GAPDH) and a 45-kDa (actin). A purified brain tubulin (Cytoskeleton) was also retained with high affinity by the E-6-BSA, but with less affinity by an E-17-BSA column and not retained by either BSA, P-3-BSA or C-21-BSA columns. E-6-[125I]BSA bound with high affinity to tubulin (1 microg) and 17beta-estradiol completely displaced the binding at 10(-7) M. 17alpha-estradiol was ineffective and neither progesterone, corticosterone, DES nor 2-methoxyestradiol (2-ME) was able to displace the ligand. The T-3-[125I]BSA also bound to tubulin. But it seems to interact with another binding site, because colchicine at 10(-5) M completely eliminated the binding of T-3-[125 I]BSA to tubulin but did not displace the E-6-BSA site. Taxol competed off both ligands but only by 50%. None of the two ligands bound actin. These novel findings add new information to be considered in the intracellular actions of estradiol, particularly in the remodeling and functions of the cytoskeleton.
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PMID:Estradiol, in the CNS, targets several physiologically relevant membrane-associated proteins. 1174 82


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