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:2.3.1.28 (chloramphenicol acetyltransferase)
5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MDA-MB-231 human breast cancer cells express the aryl hydrocarbon (Ah) receptor; however, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) does not induce CYP1A1 gene expression or chloramphenicol acetyltransferase (CAT) activity in cells transiently transfected with pRNH11c, and Ah-responsive plasmid derived from the 5'-flanking region of the human CYP1A1 gene. However, when MDA-MB-231 cells were treated with 10 nM TCDD and co-transfected with pRHN11c and a human estrogen receptor (hER) expression plasmid (delta hER), there was approximately a 10-fold increase in CAT activity. The restoration of Ah-responsiveness in MDA-MB-231 cells by expression of nuclear hER was highly specific since parallel studies in which plasmids that express the progesterone receptor and Jun nuclear proteins did not restore Ah-responsiveness to this cell line. Moreover, in cells transiently transfected with the pRNH11c and delta hER plasmids and 10 nM TCDD, overexpression of the Jun protein inhibited the effects of the hER on Ah-responsiveness. Plasmids that express truncated forms of the hER were also active in MDA-MB-231 cells but were not as effective as the complete hER. These studies reveal a unique function for the ER in MDA-MB-231 cells in which expression of this protein results in restoration of Ah-responsiveness.
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PMID:Restoration of aryl hydrocarbon (Ah) responsiveness in MDA-MB-231 human breast cancer cells by transient expression of the estrogen receptor. 820 98

The mRNA for transforming growth factor beta 3 (TGF-beta 3) includes a long (1.1-kb) 5' noncoding region which exerts a potent inhibitory effect on translational efficiency. We now report that many human breast cancer cell lines (T47-D, SK-BR-3, ZR-75-1, and BT-474) express two mRNA species for TGF-beta 3: the 3.5-kb transcript previously described as the only TGF-beta 3 mRNA species in cells and a novel 2.6-kb transcript which lacks approximately 870 nucleotides from the 5' noncoding region. The 5' end of the shorter transcript was sequenced, establishing it to be a 5' truncation of the full-length TGF-beta 3 transcript. Estradiol decreased mRNA levels of both TGF-beta 3 mRNA transcripts to an equivalent degree in estrogen receptor-positive cells. In contrast, the synthetic progestin gestodene altered the relative abundance of the two transcripts, preferentially diminishing the expression of the 2.6-kb transcript. The potential for enhanced mRNA translation attributable to the shorter 5' noncoding region was evaluated by transfection of cells with chimeric plasmid constructs in which the transcription unit consisted of coding sequence for chloramphenicol acetyltransferase downstream of the 5' noncoding sequence from TGF-beta 3. The translational efficiency of chloramphenicol acetyltransferase-encoding mRNA containing the shorter 5' noncoding region of the 2.6-kb TGF-beta 3 transcript was approximately seven times greater than with the full-length 5' noncoding region of TGF-beta 3. Polysome analysis of TGF-beta 3 mRNA in SK-BR-3 cells supported the hypothesis that the 2.6-kb transcript was more actively engaged in translation.
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PMID:Enhanced translational efficiency of a novel transforming growth factor beta 3 mRNA in human breast cancer cells. 826 30

Although the important role of thyroid hormones in regulating metamorphosis of amphibian larvae is well known, it has not been clearly established if thyroid hormones have any function in the activities of adult amphibian tissues. We now describe a strong effect of 3,3',5-triiodothyronine (T3) on adult Xenopus liver cells. Low doses of T3 rapidly (within 6-12 h) potentiate the activation of vitellogenin (Vit) genes by estradiol-17 beta (E2) in primary cultures of adult male and female Xenopus hepatocytes. This effect is developmentally regulated and is first manifested during metamorphic climax. In an attempt to explain this potentiation, we find that T3 also upregulates thyroid hormone receptor beta, but not alpha, transcripts and rapidly enhances the autoinduction of estrogen receptor (ER) mRNA in adult Xenopus hepatocytes. In transient transfection of the Xenopus cell line XTC-2 with an estrogen response element--chloramphenicol transacetylase (ERE-CAT) construct T3 was found to potentiate the transcription by E2 from the transfected ERE, thus suggesting that it enhances the accumulation of functional ER. We conclude that T3 can function in adult amphibian tissues, and discuss the significance of thyroid hormone potentiation of responses to estrogen in reproductive processes.
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PMID:Thyroid hormone potentiates estrogen activation of vitellogenin genes and autoinduction of estrogen receptor in adult Xenopus hepatocytes. 827 36

We have used a negative glucocorticoid response element (nGRE) from the bovine prolactin promoter linked to the gene for chloramphenicol acetyltransferase (PRL3CAT) to study the inhibition of gene expression by steroid hormone receptors. This nGRE increased basal expression from a heterologous promoter in COS-7 cells. In the presence of cotransfected glucocorticoid (GR), androgen, or progesterone receptor (PR) expression vectors and their cognate ligands, the expression of PRL3CAT could be repressed, indicating that these steroid receptor subfamily members could function through the same negative response element. No repression was observed with the estrogen receptor, showing that the repressive effect was specific for members of the GR-subfamily. Mutation of three amino acids within the GR-DNA binding domain that determine the specificity of GR-GRE interaction abolished the ability of the GR to inhibit the expression of PRL3CAT, demonstrating the requirement for DNA binding of the GR in the mechanism of repression. The antiglucocorticoid/antiprogestin RU486 when bound to PR or GR also repressed the expression of the PRL3CAT, but higher concentrations of RU486 were required to obtain an effect with the GR when compared to the PR. RU486 was unable to antagonize the effect of progestins on PRL3CAT and only partially antagonized the glucocorticoid repression. Thus, regarding the repression of PRL3CAT, RU486 acted as an agonist when bound to the PR and as a partial agonist when bound to the GR.
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PMID:Inhibition of gene expression by steroid hormone receptors via a negative glucocorticoid response element: evidence for the involvement of DNA-binding and agonistic effects of the antiglucocorticoid/antiprogestin RU486. 839 27

Corticotropin-releasing hormone (CRH) plays major roles in coordination of the stress response and regulation of the immune/inflammatory reaction, two important functions associated with sexual dimorphism. Two overlapping segments of the 5' flanking region of the human (h) CRH gene, the proximal 0.9 kb (containing two perfect half-palindromic estrogen-responsive elements [EREs]) and the 2.4 kb (including the former and containing two additional perfect half-palindromic EREs), were examined for their ability to confer estrogen-mediated transcriptional enhancement to a homologous or heterologous promoter. The level of estrogen-induced transactivation by the 0.9- and 2.4-kb segments was determined by chloramphenicol acetyltransferase analysis in CV-1 cells cotransfected with estrogen receptor (ER) cDNA expression plasmids, and found to be respectively approximately 10% and 20% of that of the strongly estrogen-responsive Xenopus vitellogenin A2 enhancer. Gel retardation and immunoprecipitation demonstrated specific association between the perfect half-palindromic EREs of hCRH gene and the DNA binding domain of hER in vitro. These findings may constitute the basis of sexual dimorphism in the expression of the CRH gene in the central nervous system and periphery, and might shed light in existing gender differences in stress response and immune regulation.
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PMID:Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction. 840 41

Previously, we demonstrated that the progestin components (19-nortestosterone derivatives) in oral contraceptives are able to stimulate human breast cancer cell proliferation via an estrogen receptor (ER)-mediated mechanism. We now examine RU486, an antiprogestin, to determine whether it has estrogenic properties because it is also a 19-nortestosterone derivative. We found that RU486 stimulated the growth of MCF-7 human breast cancer cells at a concentration of 10(-6) M, which is similar to the pharmacological concentration (micromolar range) found in women taking RU486. The antiestrogens 4-hydroxytamoxifen and ICI 164,384 blocked RU486-induced cell proliferation. The estrogenic activity of RU486 is not due to impurities or aromatization to estrogenic metabolites. To determine whether the proliferative action of RU486 was mediated through the ER, cells were transfected with a chloramphenicol acetyltransferase reporter gene under the control of an estrogen response element derived from the Xenopus laevis vitellogenin 2A gene. We found that RU486 was able to induce chloramphenicol acetyltransferase activity at the concentrations that stimulated cell proliferation, and this induction was blocked by the addition of 4-hydroxytamoxifen and ICI 164,384. The estrogenic potential of RU486 to regulate ER target gene expression was also investigated. We found that, like 17 beta-estradiol (E2), RU486 was able to alter the expression and synthesis of progesterone receptor. The level of progesterone receptor (145 and 186 fmol/mg cytosol protein, respectively) was increased significantly compared to the control value (3 fmol/mg cytosol protein) with the addition of 10(-6) M RU486 or 10(-10) M E2, as determined by an enzyme immunoassay. The levels of transforming growth factor-beta 2 (TGF beta 2) and TGF beta 3 mRNA, but not TGF beta 1 mRNA, were decreased dramatically with the addition of 10(-6) M RU486. This is consistent with the effects of E2 on TGF beta expression. Therefore, RU486 has estrogen-like activities in its regulation of ER target gene expression. These results demonstrate that RU486 is a weak estrogen in human breast cancer cells and suggest that the RU486-induced cell proliferation is mediated via ER. The novel finding that RU486 exhibits some estrogen-like activity may be important for the interpretation of its action at high dosages as an abortifacient and also if RU486 is going to be evaluated clinically, again at high doses, for the treatment of breast cancer.
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PMID:Estrogenic actions of RU486 in hormone-responsive MCF-7 human breast cancer cells. 850 63

17 beta-Estradiol (E2) induces cathepsin D mRNA levels and intracellular levels of immunoreactive protein in MCF-7 human breast cancer cells. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alone does not affect cathepsin D gene expression in this cell line; however, in cells cotreated with TCDD and E2, TCDD inhibited E2-induced cathepsin D mRNA levels, the rate of gene transcription, and levels of immunoreactive protein. The inhibitory responses were observed within 30 to 120 min after the cells were treated with TCDD. TCDD also inhibited E2-induced secreted alkaline phosphatase activity in aryl hydrocarbon (Ah)-responsive MCF-7 and wild-type mouse Hepa 1c1c7 cells cotransfected with the human estrogen receptor (hER) and the pBC12/S1/pac plasmid, which contains the 5' promoter region (-296/+57) of the cathepsin D gene and an alkaline phosphatase reporter gene. The E2-responsive ER/Sp1 sequence (-199 to -165) in the cathepsin D 5' region contains an imperfect GTGCGTG (-175/-181) xenobiotic responsive element (XRE); the role of this sequence in Ah responsiveness was investigated in gel electrophoretic mobility shift assays and with plasmid constructs containing a wild-type ER/Sp1 oligonucleotide or a mutant ER/Sp1-"XRE" oligonucleotide containing two C-->A mutations in the XRE sequence (antisense strand). In plasmid constructs which contained a chloramphenicol acetyltransferase reporter gene and the wild-type ER/Sp1 promoter sequence, E2-induced chloramphenicol acetyltransferase activity and mRNA levels were inhibited by TCDD whereas no inhibition was observed with the mutant ER/Sp1-"XRE" plasmids. Electrophoretic mobility shift assays showed that the nuclear or transformed cytosolic Ah receptor complex blocked formation of the ER-Sp1 complex with the wild-type but not the ER/Sp1 mutant oligonucleotide. Moreover, incubation of the wild-type bromodeoxyuridine-substituted ER/Sp1 oligonucleotide with the nuclear Ah receptor complex gave a specifically bound cross-linked 200-kDa band. These data demonstrate that Ah receptor-mediated inhibition of E2-induced cathepsin D gene expression is due to disruption of the ER-Sp1 complex by targeted interaction with an overlapping XRE.
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PMID:Molecular mechanism of inhibition of estrogen-induced cathepsin D gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in MCF-7 cells. 852 36

We have previously demonstrated sex-specific stimulation of creatine kinase specific activity (CK) in bone cells both in vivo and in vitro, in primary culture cells derived from rat and human bone and in established human bone-derived cell lines. We found that the female-derived cell line, SaOS-2, responded to 17 beta-estradiol (E2) by increased CK specific activity. The effects of E2 on the CK activity in SaOS-2 cells was inhibited by 100-fold excess of 4-hydroxytamoxifen (Tam) as well as by the other antiestrogen, ICI 164,384. Tam by itself had some stimulatory effect whereas ICI 164,384 showed no estrogenic activity. We also demonstrated the estrogenic-like effect of another anti-estrogen, raloxifene (Ral), which is agonist only in the SaOS-2 osteoblast-like cells but not in the human endometrial, Ishikawa cell line. Ishikawa cells respond to E2 and to Tam by increased CK activity. In both osteoblasts and endometrial cell lines, Ral and Tam were inhibitory in the presence of E2. The effects of E2 on SaOS-2 cells are at least partially mediated by the estrogen receptor (ER) at the level of transcription as demonstrated by transient transfection experiments using the human creatine kinase promoter chloramphenicol acetyltransferase in these cells. Pretreatment of SaOS-2 with calcitropic hormones, either 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) or human parathyroid hormone (1-34) (hPTH(1-34)) increased the stimulation of CK by E2 by 40-60% relative to E2 alone and significantly increased the sensitivity of the cells to E2 by lowering the effective hormonal dose needed for stimulation of CK by E2 by 100-fold. This stimulatory effect of pretreatment of the cells with 1,25(OH)2D3 was due to a 2.5-fold increase in the level of ER expression as measured directly by enzyme immunoassay in the SaOS-2/1 subline. The increase in the responsiveness to E2 by hPTH(1-34) was not due to an increase in ER level in the cells. We can conclude that in cell cultures as in vivo, Ral shows different effects depending on the cell type, namely estrogenic-like activity in skeletal cells but not in uterine cells. We can also conclude that as with rat-derived cells, in bone cells derived from human bone 1,25(OH)2D3 increased the sensitivity to E2 due to an increase in the number of ER in the cells, whereas PTH(1-34) augmented the response to E2 without increasing ER, by another, as yet unknown, mechanism. These studies suggest that the treatment of pathological bone disorders may be improved by combined hormone therapy.
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PMID:Stimulation of creatine kinase specific activity in human osteoblast and endometrial cells by estrogens and anti-estrogens and its modulation by calciotropic hormones. 886 94

The antiestrogenic activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated in several cell lines using transient transfection assays and constructs containing 5'-regulatory sequences from the estrogen (E2)-responsive vitellogenin (Vit) A2 gene linked to the bacterial chloramphenicol acetyltransferase (CAT) reporter gene. TCDD significantly inhibited CAT activity induced by E2 in MCF-7 human breast cancer cells transiently transfected with 5'-deletion plasmids containing the homologous promoter [(-821/+14)- and (-482/+14)-CAT] or the heterologous thymidine kinase (tk) promoter [(-821/-87)tk-, (-482/-87)tk-, (-397/-87)tk-, and (-331/-87)tk-CAT]. In parallel experiments using wild-type mouse Hepa 1c1c7 and human HeLa cells cotransfected with a human estrogen receptor expression plasmid, TCDD also inhibited E2-induced CAT activity. The role of the nuclear Ah receptor complex was confirmed by results of the following studies using MCF-7 or mouse Hepa 1c1c7 cells transiently transfected with E2-responsive Vit A2 gene 5'-promoter constructs: (i) for a series of Ah receptor ligands, there was a correlation between their antiestrogenic activity in MCF-7 cells and their rank order binding affinity for the Ah receptor; (ii) alpha-naphthoflavone, an Ah receptor antagonist, inhibited the antiestrogenic activity of TCDD in MCF-7 cells; and (iii) TCDD inhibited E2-induced CAT activity in Ah-responsive wild-type but not in Ah-nonresponsive class 2 mutant Hepa 1c1c7 cells. The antiestrogenic activity of TCDD was also observed in cells which transiently overexpressed the human estrogen receptor (ER), suggesting that the mechanism does not involve downregulation of the ER by TCDD.
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PMID:Inhibition of estrogen-induced activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the MCF-7 human breast cancer and other cell lines transfected with vitellogenin A2 gene promoter constructs. 901 89

Hepatocyte growth factor (HGF) is a multifunctional cytokine that controls the growth and differentiation of various tissues. Previously, we described the existence of a negative cis-acting regulatory element(s) within the -1- to -0.7-kilobase pair (kb) portion of the 5'-flanking region of the mouse HGF promoter. In the present study, we show that the repressor element is located at position -872 to -860 base pairs and comprises an imperfect estrogen-responsive element 5'-AGGTCAGAAAGACCA-3'. We demonstrate that chicken ovalbumin upstream promoter transcription factor (COUP-TF), a nuclear orphan receptor belonging to the steroid/thyroid hormone receptor superfamily, through binding to this site effectively silences the transcriptional activity of the HGF promoter. We show that estrogen receptor, on the other hand, relieves the repressive action of COUP-TF, resulting in the induction of the HGF promoter. Using mice transgenic for either 2.7 or 0.7 kb of the HGF promoter region linked to the chloramphenicol acetyltransferase reporter gene, we found that injection of estradiol stimulates HGF promoter activity in tissues such as the mammary gland and ovary of mice harboring 2.7 but not 0.7 kb of the mouse HGF promoter region. Potential involvement of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors in the regulation of HGF gene expression is also discussed.
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PMID:Transcriptional regulation of the hepatocyte growth factor gene by the nuclear receptors chicken ovalbumin upstream promoter transcription factor and estrogen receptor. 902 96


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