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Titolo:
NGF, CYCLIC-AMP, AND PHORBOL ESTERS REGULATE OXYTOCIN RECEPTOR GENE-TRANSCRIPTION IN SK-N-SH AND MCF7 CELLS
Autore:
BALE TL; DORSA DM;
Indirizzi:
UNIV WASHINGTON,DEPT PHARMACOL,BOX 357280 SEATTLE WA 98195 UNIV WASHINGTON,DEPT PSYCHIAT & BEHAV SCI SEATTLE WA 98195
Titolo Testata:
Molecular brain research
fascicolo: 1-2, volume: 53, anno: 1998,
pagine: 130 - 137
SICI:
0169-328X(1998)53:1-2<130:NCAPER>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-C; LIGHT MICROSCOPIC AUTORADIOGRAPHY; HYPOTHALAMIC VENTROMEDIAL NUCLEUS; MESSENGER-RIBONUCLEIC-ACID; RAT-BRAIN; BINDING-SITES; MATERNAL-BEHAVIOR; ESTROUS-CYCLE; RABBIT AMNION; SEXUAL RECEPTIVITY;
Keywords:
OXYTOCIN RECEPTOR; PROMOTER; TRANSFECTION; SK-N-SH; MCF7; PHORBOL 12-MYRISTATE 13-ACETATE; FORSKOLIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
50
Recensione:
Indirizzi per estratti:
Citazione:
T.L. Bale e D.M. Dorsa, "NGF, CYCLIC-AMP, AND PHORBOL ESTERS REGULATE OXYTOCIN RECEPTOR GENE-TRANSCRIPTION IN SK-N-SH AND MCF7 CELLS", Molecular brain research, 53(1-2), 1998, pp. 130-137

Abstract

Oxytocin receptor (OTR) gene transcription has predominantly been thought to be regulated by estrogen. However, the continuous presence of receptors in certain brain regions after gonadectomy suggests the existence of alternate mechanisms of regulation. We have cloned and sequenced 4 kb of 5'-flanking DNA of the rat OTR gene and identified an internal segment which was absent in the initial publication of this promoter sequence. Sequence analysis of this segment, as well as of a novelupstream region, revealed the presence of a CRE as well as several other potential regulatory elements, including AP-1, AP-2, AP-3, AP-4 sites, an ERE, and a half-SRE (SRE/2). The effects of phorbol 12-myristate 13-acetate (PMA), forskolin, and NGF treatment on this promoter were tested in transfection experiments in MCF7 and SK-N-SH cells. Transcription of the full-length OTR promoter was induced by forskolin and by the phorbol ester PMA, and a synergistic (17-fold) effect was observed in MCF7 cells treated with both agents. Receptor binding studies using the OTR antagonist I-125-labeled ornithine vasotocin, and Western blot analyses of OTRs in MCF7 cells, showed that PMA and forskolin also increased the density of endogenous human oxytocin receptors. Mutational analyses of the CRE and half-SRE sites in this promoter indicatedthat these elements function as enhancers and support forskolin and NGF effects, respectively, on transcription. These studies have identified a novel region of the rat OTR promoter containing elements which impart cAMP and/or phorbol ester inducibility of OTR gene transcription. A potential role of the PKA and/or PKC pathways in OTR gene regulation is suggested. (C) 1998 Elsevier Science B.V.

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Documento generato il 06/04/20 alle ore 08:29:45