Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies were performed to determine whether ARP-1, which is an orphan receptor of the steroid receptor superfamily, inhibits basal activity of the human placental lactogen (hPL) promoter and the increase in hPL promoter activity in response to the receptors for thyroid hormone (TR) and retinoic acid (RAR). Co-transfection of an ARP-1 expression vector into BeWo choriocarcinoma cells, along with an expression vector containing 1.2 kb of the hPL promoter coupled to a CAT reporter gene, resulted in a dose-dependent inhibition of basal CAT activity. In addition, ARP-1 inhibited the stimulation of CAT activity by RAR alpha and TR beta expression vectors. Mobility shift assays demonstrated that ARP-1 binds specifically to a composite steroid response element on the hPL promoter that confers retinoic acid and T3 responsiveness. The results implicate an inhibitory role for ARP-1 in the regulation of hPL gene expression and strongly suggest that hPL gene expression is regulated, at least in part, by the interaction of stimulatory and inhibitory members of the steroid receptor superfamily.
J Mol Endocrinol 1996 Jun
PMID:The ARP-1 orphan receptor represses steroid-mediated stimulation of human placental lactogen gene expression. 878 80

The type 2 isoform of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD2), which catalyzes the conversion of cortisol to hormonally inactive cortisone in man, is principally expressed in the placenta and mineralocorticoid target tissues, kidney and colon. To date, few studies have addressed the regulation of this novel 11 beta-HSD2 isoform. We have characterized the nature and regulation of the 11 beta-HSD activity expressed in a human cytotrophoblastic cell line, the JEG-3 choriocarcinoma cell. The 11 beta-HSD activity in JEG-3 cell homogenates required NAD+ as cofactor with NADP+ ineffective and demonstrated a high affinity for cortisol (apparent Km 31 nM). Incubation of JEG-3 cells with forskolin and dibutyryl cyclic AMP increased 11 beta-HSD2 activity several-fold in a time-dependent manner, while treatment with phorbol ester had little, if any, effect on 11 beta-HSD2 activity. Northern blot analysis of RNA isolated from JEG-3 cells after these treatments demonstrated a marked increase in a 1.9 kb 11 beta-HSD2 mRNA species in cells treated with forskolin for 24 h. We conclude that 11 beta-HSD2 is regulated by activation of the protein kinase A pathway, but not the protein kinase C pathway in human choriocarcinoma cells, and that this regulation occurs at a pretranslational level. JEG-3 cells provide an excellent model for further studies on the regulation of 11 beta-HSD2 gene expression in human trophoblast tissue.
J Mol Endocrinol 1996 Jun
PMID:Regulation of 11 beta-hydroxysteroid dehydrogenase type 2 activity and mRNA in human choriocarcinoma cells. 878 85

The NAD+ dependent (K or type 2) isozyme of 11 beta-hydroxysteroid dehydrogenase oxidizes glucocorticoids and thus prevents them from occupying mineralocorticoid receptors. Mutations in the HSD11K (HSD11B2) gene encoding this isozyme cause a genetic form of hypertension, the syndrome of apparent mineralocorticoid excess (AME). This isozyme is expressed at high levels in placenta and kidney but is undetectable in liver. We have now analyzed the proximal 1788 nucleotides (nt) of the 5' flanking region of the HSD11K gene to identify transcriptional regulatory elements that are active in JEG-3 human choriocarcinoma cells. Using luciferase reporter constructs, the region from -2 to -330 nt relative to the initial ATG codon was identified as an essential region for basal transcription of the HSD11K gene. Two segments in this region, -278 to -257 and -215 to -194. were protected in DNase 1 footprinting analysis. Both segments have consensus binding sites for the Spl transcription factor. Gel shift assays of these segments show several DNA-protein complexes using JEG-3 nuclear extract. Only the slowest migrating complex was competed by an antiserum to Spl. These results suggest that the two Spl sites, either alone or in combination, are essential for transcription of the HSD11K gene in JEG-3 cells.
Mol Cell Endocrinol 1996 Jul 23
PMID:Analysis of the promoter of the NAD+ dependent 11 beta-hydroxysteroid dehydrogenase (HSD11K) gene in JEG-3 human choriocarcinoma cells. 886 70

The structure and expression of a clone containing the promoter region, all of exon 1, and part of the first intron of the human mineralocorticoid receptor (hMR) gene is presented. The clone has three sets of CAAT and TATA elements, one located at the very 5'-end of the clone, one located just 5'- to the start of transcription, and one set located in intron A, approximately 300 bp into the intron. The major start of transcription site by primer extension analysis and ribonuclease protection assays is located 26 bp downstream of a TATA-like box (TTTAA) and 90 and 143 bp downstream, respectively, of two CCAAT boxes. Putative cis-transcription factor binding sites are as follows: two potential AP1 sites, one potential AP2 site, two ATF/CREB sites, six potential GC boxes or SP1 sites, one potential perfect half-palindromic estrogen response element, and three potential PEA3 sites. Therefore, the hMR promoter region contains elements characteristic of both regulated genes and "housekeeping" genes. CAT assays of overlapping deletions of the promoter region demonstrated tissue-specific regulation in human neuroepithelioma (SK-N-MC-IXC) and non-neuronal, peripheral choriocarcinoma cell lines (JEG-3).
J Steroid Biochem Mol Biol 1996 Aug
PMID:The human mineralocorticoid receptor gene promoter: its structure and expression. 891 75

We examined four choriocarcinoma cell lines, NaUCC-1, NaUCC-3, NaUCC-4 and BeWo, for the presence of epidermal growth factor (EGF) by enzyme immunoassay and reverse transcription and polymerase chain reaction, and for EGF receptor (EGFR) by 125I-EGF binding assay. Specific EGF binding and EGF proteins were detected in these four choriocarcinoma cell lines. On the cell lines examined, NaUCC-4 had the greatest EGF binding capacity (18 x 10(5) sites/cell) and the highest amount of immunoreactive EGF (142 pg/ml). These results prompted us to assess the significance of EGF/EGFR autocrine mechanism in NaUCC-4 cells. Low doses of exogenous EGF stimulated 3H-thymidine incorporation, and monoclonal antibodies against EGF or EGFR dose-dependently inhibited 3H-thymidine incorporation. On the other hand, these antibodies did not significantly affect hCG production. These results suggested that EGF might function in an autocrine manner to stimulate proliferation rather than differentiation of NaUCC-4 choriocarcinoma cells.
Mol Cell Endocrinol 1996 Nov 29
PMID:Autocrine mechanism of epidermal growth factor in choriocarcinoma cell proliferation. 902 25

Thyroid hormone (T3) modulates the mRNA levels for cytochrome c and the adenine nucleotide translocator-2 (ANT2) in adult rat liver. Here we show that T3 activates expression of a reporter gene driven from the human cytochrome c1 and ANT2 promoters transfected into human choriocarcinoma JEG3 cells. By contrast, the human F1-ATPase beta-subunit promoter responded marginally, thus providing a pattern of differential expression similar to that earlier observed in rats in vivo. T3-activation is dependent on co-expression of the thyroid hormone receptor (TR alpha1). Co-expression of both the TR and RXR receptors had no additional effect. Transient transfection of deletion constructs showed that T3 activation is retained by the proximal regions of the cytochrome c1 and ANT2 promoters, and, in the case of cytochrome c1, is lost upon removal of a fragment containing the transcription initiator ((nucleotides) (nt) + 1 to + 100). The promoter regions supporting T3-activation of the reporter genes appear to lack strong DNA binding sites for TR and retinoid X receptor (RXR).
Mol Cell Endocrinol 1997 Apr 04
PMID:Thyroid hormone activates transcription from the promoter regions of some human nuclear-encoded genes of the oxidative phosphorylation system. 914 77

A transcriptional enhancer which has a consensus binding sequence for transcription enhancer factor-1 (TEF-1) has been found 3' of the hPL(3) gene. We examined whether TEF-1 is expressed by the human placenta and whether such expression is co-ordinated with that of human placental lactogen (hPL). Probing Northern blots of total RNA from first trimester and term placenta, the choriocarcinoma-derived cell line JAr and primary cultured cytotrophoblast cells with a cDNA for TEF-1 revealed transcripts of 12-13 kb and 3-4 kb. The level of TEF-1 expression was the same in first trimester as compared with term placenta and in undifferentiated JAr as compared with differentiated cytotrophoblast cells. hPL expression was tenfold higher in term compared with first trimester placenta and, whilst detectable in cytotrophoblast cells, was undetectable in JAr cells. These data show that TEF-1 is expressed by the placenta but is not co-ordinated with hPL expression.
J Mol Endocrinol 1996 Apr
PMID:The human placenta expresses transcription enhancer factor-1 but there is no correlation with the expression of placental lactogen. 915 23

A bovine trophoblast interferon (IFN-tau) gene promoter sequence (-450 to +26 bp relative to the transcription start site) led to expression of reporter gene (CAT) constructs transfected into L929 (murine fibroblast) or JAR (human choriocarcinoma) cells. Expression depended on the presence of an exogenous (SV40) enhancer. Poly(I)(C) activated endogenous IFN production in L929 and JAR cells but had no consistent effect on CAT expression. Similar results were obtained in L929 cells with inactivated Newcastle disease virus. There was no 'priming' effect of exogenous Type I IFN. Deletion mutants revealed sites exerting negative control on expression between - 338 and - 247 bp, and between - 150 and - 71 bp; these regions contained sequences resembling previously identified negative regulatory domains. In the absence of viral inducibility it is proposed that negative regulation contributes towards the stringent control of expression characteristic of IFN-tau genes.
J Mol Endocrinol 1996 Apr
PMID:Negative regulatory domains in a trophoblast interferon promoter. 915 24

During the first trimester of pregnancy, the human placental trophoblast contains very low levels of choline acetyltransferase (ChA), a specific enzyme for synthesis of acetylcholine (ACh) and a reliable cholinergic marker. There is a relationship between ChA levels and development and maturation of syncytiotrophoblast during the first six months of pregnancy, when ChA levels reach maximum. These observations suggest that ChA and its product, ACh, have significant roles during differentiation of cytotrophoblast into syncytium. Therefore, we have measured ChA levels in malignant trophoblast cultures before and after differentiation. Two pure trophoblast cell lines (BeWo and JAr) are used in these studies. ChA in these cells was determined by a standard radiometric method in which 14C-acetyl groups were transferred from 14C-acetylcoenzyme A to choline. Methotrexate (1 microM) was used to differentiate the cells. The following results were obtained: 1) Undifferentiated BeWo cells contained ChA level of 311.0 +/- 8.3 pmoles ACh formed (M +/- S.E., N = 6)/mg protein/10 min. Differentiation decreased ChA level to 213.0 +/- 9.3 pmoles ACh/mg protein/10 min.; b) Undifferentiated JAr cells contained ChA levels of 279.0 +/- 15.0 ACh pmoles formed/mg protein/10 min. This decreased to 166.8 +/- 10.0 upon differentiation; c) Upon differentiation, ChA levels decreased by 31.5-40.2% in BeWo and JAr cell lines. In term human placenta, the ChA levels falls by about 46.0-73% after syncytiotrophoblast is fully developed; d) Chorionic gonadotropin (hCG), which is produced in cytotrophoblast, is a standard tumor marker for chorionic cancer. As the syncytiotrophoblast is formed, production of hCG decreases. Similarly, production of hCG by BeWo and JAr cells decreases upon their differentiation, and e) In hydatidiform mole, which can undergo malignant transformation into choriocarcinoma, there were no significant levels of ChA. These observations suggest that ChA and ACh are necessary for development and maturation of syncytiotrophoblast.
Cell Mol Biol (Noisy-le-grand) 1997 Jun
PMID:Cholinergic markers in transformed trophoblast cells: BeWo and JAr cells. 922 Jan 49

Steroidogenic factor-1 (SF-1), also known as adrenal-4-binding protein (Ad4BP), is a recently-described transcription factor, which has been shown to be important for the differentiation of steroidogenic tissues. In addition, SF-1 has been implicated in regulating the glycoprotein hormone alpha-subunit gene in a pituitary gonadotroph cell line. Considering that the human placenta produces both steroids and human chorionic gonadotrophin (HCG), we studied the expression of SF-1 in this tissue. Human first trimester and term placentas were collected at the time of therapeutic abortion and birth respectively. Messenger RNA was extracted, reverse transcribed, and used for polymerase chain reaction (PCR) amplification with primers specific for the human SF-1 cDNA sequence. A band of the expected size was obtained from both first and third trimester samples, indicating that SF-1 expression in the human placenta starts early in pregnancy and is maintained until birth. In addition to normal placental samples, JEG3 and JAR choriocarcinoma cells were also analysed and found to express SF-1 mRNA. The identity of the amplified products was confirmed by diagnostic restriction digest and Southern hybridization. SF-1 protein was localized mainly to the nuclei of the cyto- and syncytiotrophoblast and to some mesenchymal villous nuclei by immunocytochemistry using a specific antibody. We conclude that SF-1 is expressed in human first trimester and term placenta, where it could be implicated in the regulation of HCG production, in steroidogenesis, or both.
Mol Hum Reprod 1996 Jun
PMID:Expression of steroidogenic factor-1 (SF-1) mRNA and protein in the human placenta. 923 16


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