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)

The expression of the principal opioid peptide gene, preproenkephalin A, is exquisitely regulated by primary afferent inputs to the spinal and medullary dorsal horns. This regulated expression in response to neural synaptic activity has been referred to as trans-synaptic regulation. To define which DNA regions could mediate this trans-synaptic regulation, transgenic 'HEC' mice whose genomes include 193 bp of the human preproenkephalin A promoter fused to a chloramphenicol acetyltransferase (CAT) reporter gene were studied. Mice received unilateral electrical stimulation of the trigeminal ganglion or adjuvant injection into the hindpaw, stimuli known to regulate dorsal horn proenkephalin expression in vivo. CAT activity conferred by this promoter displayed trans-synaptic upregulation with both stimuli. Although the level of the upregulation was 2- to 3-fold higher than the change in the wild type gene, several features of this induction paralleled aspects of the behavior of the wild-type gene: the rapidity of responses to trigeminal ganglion stimulation, the stimulation intensity dependence of responses to trigeminal ganglion stimulation and the time course of upregulation noted following adjuvant injection. Regulatory proteins binding to this restricted promoter region are thus likely to mediate aspects of dorsal horn enkephalin regulation by pain and other somatic stimuli.
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PMID:Primary afferent stimulation acts through a 193 base pair promoter region to upregulate preproenkephalin expression in dorsal horn of transgenic mice. 131 94

The regulation and possible function of the preproenkephalin gene in testis were studied in vivo in transgenic mice containing: (1) bases -193 to +210 of the human proenkephalin gene and an additional one kilobase of 3' proenkephalin flanking sequence driving expression of bacterial chloramphenicol acetyltransferase (CAT), and (2) the same promoter and flanking sequences driving expression of a rat proenkephalin cDNA. Five lines of mice, designated HEC1-5, expressed the first construct and 10, HER1-10, the second. Each HEC male and many HER males showed dramatic expression of the transgene in the testis, although much lower expression was observed in the brain and other enkephalin-producing tissues. High levels of expression in testis can thus be achieved with a very short promoter region and do not require intron A sequences previously considered necessary. Altered enkephalin expression may affect testicular function. One founder, HER8, displayed grossly abnormal testicular morphology and was completely infertile. A second founder, HER6, had low sperm motility. Two offspring from other lines also displayed subnormal fertility. These studies support a role for specific promoter sequences in testis expression and may further support a significant role for proenkephalin in testicular function.
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PMID:Proenkephalin transgenic mice: a short promoter confers high testis expression and reduced fertility. 791 79

The involvement of altered c-jun activity in medroxyprogesterone acetate (MPA)-induced growth responses in human endometrial carcinoma cells is examined in this paper. Under conditions of MPA-induced growth inhibition, c-jun mRNA and protein levels are decreased in Ishikawa cells. This decrease is accompanied by an overall decrease in endogenous AP-1 activity in these cells. Only a transient decrease in c-jun mRNA level without any effect on endogenous AP-1 activity is seen in HEC-50 human endometrial carcinoma cells after MPA treatment. Increased expression and activity of c-jun was achieved in Ishikawa cells by transient transfection of Rous sarcoma virus (RSV)-c-jun alone or RSV-c-jun plus AP-1 binding sites (5x-4-beta-phorobol 12-myristate 13-acetate response element-thymidine kinase-chloramphenicol acetyltransferase), respectively. These treatments were accompanied by an increase in cell numbers due to MPA treatment in Ishikawa cells. In contrast, MPA treatment of mock-transfected, RSV-jun-B-transfected, or 5x-4 beta-phorbol 12-myristate 13-acetate response element-thymidine kinase-chloramphenicol acetyltransferase alone transfected Ishikawa cells resulted in the expected decrease in cell numbers. The data presented in this paper are consistent with the hypothesis that altered c-jun activity in a target cell can alter proliferative responsiveness to MPA and suggest that such a mechanism may be associated with resistance to hormonal manipulative therapies used in the treatment of both human breast and endometrial cancer.
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PMID:Enhanced c-jun activity alters responsiveness to medroxyprogesterone acetate in Ishikawa human endometrial carcinoma cells. 814 69

Growth factor regulation of normal and cancerous cell proliferation has been well-documented and may be mediated by proto-oncogene activity. The purpose of this study was to assess changes in proliferation and mitogen-induced c-fos mRNA expression of an endometrial carcinoma cell line, HEC-1-A, in response to TGF-beta, a potent growth-inhibitory peptide. HEC-1-A cells were incubated in the presence or absence of TGF-beta. Mitogen-stimulated cells were additionally treated with epidermal growth factor (EGF). Changes in proliferation were measured by [3H]thymidine uptake assays. Alterations in EGF-induced c-fos expression following TGF-beta pretreatment were assessed by Northern blot using a 32P-labeled human c-fos probe. Finally, chloramphenicol acetyltransferase assays were performed to evaluate c-fos promoter activity in response to treatment conditions. Basal and EGF-stimulated proliferation was inhibited by TGF-beta in a dose- and time-dependent manner. TGF-beta also reversibly decreased EGF-induced c-fos mRNA expression in a dose- and time-dependent manner. Sequences in the c-fos promoter that were stimulated by EGF showed suppressed activity when preincubated with TGF-beta. These results show that TGF-beta negatively modulates EGF-induced c-fos expression, which may be related to the observed inhibition of carcinoma cell proliferation.
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PMID:Transforming growth factor-beta negatively modulates proliferation and c-fos expression of the human endometrial adenocarcinoma cell line HEC-1-A. 910 92

The lactoferrin gene in the mouse uterus is a target gene for natural estrogens and xenoestrogens. One of the xenoestrogens is methyoxychlor, an insecticide that displays both estrogenic and antiandrogenic activities. Recently, methyoxychlor was found to stimulate lactoferrin gene expression in the uterus of an estrogen receptor null mouse. The present study is designed to uncover the methoxychlor response region in the mouse lactoferrin gene promoter. A series of different lengths of the mouse lactoferrin gene 5' flanking region were linked to a chloramphenicol acetyltransferase (CAT) reporter construct and transfected into human endometrial carcinoma HEC-1B cells, an estrogen receptor null cell line, in order to examine the methoxychlor response. The transfected cells were treated with methoxychlor or the metabolite of methoxychlor, HPTE, and the CAT reporter activities were measured. Constructs that contain a mouse lactoferrin 5' region longer than 100 bp were activated more than twofold by both methoxychlor and HPTE. The activation of the CAT reporter by the chemicals was dose dependent and reached saturation. Additional deletion mutants within the 100-bp region were tested, and a GC-rich sequence (GC-II) that we have previously characterized as an epidermal growth factor (EGF) response element was identified to be the region for the methoxychlor response. GC-II binds Sp1, Sp3, and IKLF transcription factors, collaborates with the AP1/CREB binding element, and confers the EGF response. Whether the effect of methoxychlor requires the AP1/CREB binding element has yet to be established; however, the present finding provides an alternative signaling pathway for the xenoestrogens.
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PMID:Methoxychlor stimulates the mouse lactoferrin gene promoter through a GC-rich element. 1190 39