Negative modulator of the rat D2 dopamine receptor gene

Minowa, Takashi; Minowa, Mari T.; Mouradian, M. Maral

doi:10.1016/s0021-9258(19)78175-7

Cited by 48 publications

(2 citation statements)

References 27 publications

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“…The present study was partially supported by research grants from Associazione Italiana Ricerca sul Cancro (AIRC) and from Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena (Milan, Italy). multiple Sp1 binding sites and consensus sequences for AP1 and AP2 are present (8). Interestingly, a retinoic acid (RA)response element (RARE) that binds RA receptors (RARa, RARb and RARc) and retinoid X receptors (RXRa, RXRb and RXRc) as RAR-RXR heterodimers in the promoter region of D2R has been identified (9).…”

Section: Introductionmentioning

confidence: 99%

Effect of 9-cis Retinoic Acid on Dopamine D2 Receptor Expression in Pituitary Adenoma Cells

Bondioni

Angioni

Corbetta

et al. 2008

Exp Biol Med (Maywood)

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The dopamine receptor subtype 2 (D2R) promoter contains a functional retinoic acid response element involved in the control of D2R expression. The aim of the study was to evaluate the effect of 9-cis retinoic acid (9-cis RA) on D2R protein expression in human pituitary adenomas and GH3 cell line. Treatment with 9-cis RA (100 nM for 48 hrs) caused a 109 +/- 32% increase of basal D2R levels in five of eight growth hormone (GH)-secreting adenomas (GH-omas), a 129 +/- 28% increase in 7 of 11 nonfunctioning adenomas, and no effect in two resistant prolactinomas by Western blotting. The lack of D2R induction in some tumors was not associated with a different pattern of retinoid x receptor (RXR) and retinoic acid receptor (RAR) isoform expression that was similar in all tumors by immunohistochemistry. While the induction of D2R did not affect the slight but significant inhibitory effect exerted by dopamine (10 nM) on in vitro GH release by GH-oma cultured cells, in pituitary GH3 cell lines cis-9 RA enhanced the dopamine-induced inhibition of in vitro GH release (% inhibition: 16 +/- 2 versus 26 +/- 5, P < 0.05), cell proliferation (25 +/- 2% versus 44 +/- 5%, P < 0.05) and cell viability (16 +/- 0.8% versus 29 +/- 1%, P < 0.05), likely by activating caspase-3 (28 +/- 3% versus basal, P < 0.05). In conclusion, this study provides novel evidence for a permissive role of retinoids on the expression of D2R in a good proportion of pituitary tumors and on the generation of pro-apoptotic signals in GH3 cell line.

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Section: Introductionmentioning

confidence: 99%

Effect of 9-cis Retinoic Acid on Dopamine D2 Receptor Expression in Pituitary Adenoma Cells

Bondioni

Angioni

Corbetta

et al. 2008

Exp Biol Med (Maywood)

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“…The promoters for these genes lack conventional CAAT and TATA sequences, but each possesses "GC" boxes reminiscent of "housekeeping" gene promoters [for review, see Mouradian et al (1994)]. However, the D1 and D2 genes are both tissue-specific and under a high degree of transcriptional regulatory control (Mouradian et al, 1994;Minowa et al, 1993;Minowa et al, 1994).…”

mentioning

confidence: 99%

The Human Dopamine D5 Receptor Gene: Cloning and Characterization of the 5'-Flanking and Promoter Region

Marchese²,

Meador-Woodruff³

et al. 1995

Biochemistry

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Genomic and overlapping cDNA clones encompassing the entire 5'-untranslated region of the human D5 receptor gene were cloned and sequenced. Comparison of these human D5 receptor genomic and cDNA clones revealed the presence of two exons separated by a small and variably sized intron (of either 179 or 155 bp). We have determined that the major site of transcription initiation of the D5 gene is 2125 bp upstream from the translational initiation start site. The region 5' to the transcription initiation site lacked conventional TATA and CAAT sequences, but contained several putative binding sites for transcription factors, such as Sp1 and Ap1. Luciferase reporter gene constructs containing D5 gene sequence information up to 500 bp 5' of the transcription initiation site were able to stimulate transcription only in SK-N-SH cells but not in COS-7, CHO, P19EC, NB41A3, and SK-N-MC cell lines. Promoter deletion analysis indicated that the D5 gene promoter contained a positive modulator at 119-182 and a negative modulator 251-500 bases upstream from the site of transcription initiation. In addition, in order to detect the expression of functional D5 receptor mRNAs and not those of its expressed pseudogenes, in situ hybridization analysis of monkey and human brain using a 5' D5-specific riboprobe revealed that D5 receptor mRNA was most abundant in discrete cortical areas (layers II, IV, and VI), the dentate gyrus, and hippocampal subfields with very little message detected in the striatum. Unexpectedly, D5 mRNA antisense riboprobes labeled discrete cell bodies in the pars compacta of the substantia nigra. The characterization of the genomic organization of the D5 receptor gene and of those factors involved in its transcriptional regulation may aid in our understanding of the role this gene product plays in the generation and maintenance of dopamine D1-like receptor-mediated events.

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Differential regulation of D2 receptor gene expression by transcription factor AP-1 in cultured cells

Wang¹,

Miller²,

Friedhoff³

1997

J. Neurosci. Res.

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The role of the transcription factor AP-1 in regulating D2 receptor transcriptional activity was investigated in D2 receptor expressing neuroblastoma cells, NB41A3, and in non-D2 receptor expressing CHO cells. Deletion of a region containing the putative AP-1 binding site resulted in a significant reduction in the activity in CHO cells; while the activity in NB41A3 cells was increased suggesting that the AP-1 site may differentially regulate D2 gene expression in these distinct cell types. However, both cell lines were found to express significant and similar levels of the transcription factors AP-1. Analysis of phosphorylated proteins in each of the cell lines provided evidence that AP-1 is phosphorylated in NB41A3 cells, but not in CHO cells. This result suggests that differential regulation of D2 gene expression may be related to AP-1 phosphorylation.

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Negative modulator of the rat D2 dopamine receptor gene

Cited by 48 publications

References 27 publications

Effect of 9-cis Retinoic Acid on Dopamine D2 Receptor Expression in Pituitary Adenoma Cells

Effect of 9-cis Retinoic Acid on Dopamine D2 Receptor Expression in Pituitary Adenoma Cells

The Human Dopamine D5 Receptor Gene: Cloning and Characterization of the 5'-Flanking and Promoter Region

Differential regulation of D2 receptor gene expression by transcription factor AP-1 in cultured cells

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