Effect of κ opioid agonist RU 51599 on osmotic and non-osmotic stimulated arginine vasopressin release and gene regulation in small cell lung carcinoma cells

Kim, J.K; Summer, Sandra N.; Schrier, Robert W.

doi:10.1016/s0143-4179(97)90035-4

Cited by 3 publications

(2 citation statements)

References 36 publications

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“…Key words : lung tumour, neuropeptide, transcription, tumourspecific, upstream stimulatory factor. the level of AVP synthesis or secretion [7]. There is, however, persuasive clinical evidence that AVP expression in SCLC is not subject to the normal osmotic regulation, as AVP production continues despite dilutional hyponatraemia.…”

Section: Introductionmentioning

confidence: 99%

E-box motifs within the human vasopressin gene promoter contribute to a major enhancer in small-cell lung cancer

Coulson

Fiskerstrand

Woll

et al. 1999

Biochemical Journal

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[Arginine]vasopressin (AVP) is a neuropeptide physiologically synthesized in the hypothalamus but pathologically expressed by small-cell lung cancer (SCLC). A minimal 65 bp AVP promoter can restrict basal activity to SCLC in vitro, but a 199 bp fragment directs 5-fold higher expression in SCLC [Coulson, Stanley and Woll (1999) Br. J. Cancer 80, 1935-1944]. Several predicted E-box motifs occur within the 199 bp fragment, and we now describe an enhancer which contributes to AVP promoter tumour-specificity in some cell lines. The deletion of two adjacent E-boxes (-157 to -131) resulted in an approx. 70% loss of reporter gene expression in a SCLC line (Lu-165) with high endogenous AVP production. Using a series of AVP promoter deletion constructs and site-directed mutagenesis, we show that both these E-box sites were required for enhancer function, whereas mutation of an adjacent AP-1 site had no effect on the promoter activity. Electrophoretic-mobility-shift analysis indicated that, although both the predicted E-box motifs bound specific complexes, only one appeared to function as a strong E-box which binds basic helix-loop-helix (bHLH) factors. This motif formed a complex in lung tumour-cell extracts, which was particularly strongly bound in Lu-165, and was competed for by a characterized E-box motif from the preprotachykinin A promoter. Antibody supershifts indicate that this complex is a heterodimer of upstream stimulatory factor (USF)-1 and USF-2. Non-bHLH complexes weakly bound the second potential E-box motif in a SCLC-specific manner. These complexes were not recognized by the bHLH antibodies and remain unidentified; however, they were detected in seven of eight SCLC cell lines and not in four control lines. We postulate that there is a co-operative and complex interaction between an E-box and an adjacent site constituting a SCLC-specific enhancer within the AVP proximal promoter.

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Section: Introductionmentioning

confidence: 99%

E-box motifs within the human vasopressin gene promoter contribute to a major enhancer in small-cell lung cancer

Coulson

Fiskerstrand

Woll

et al. 1999

Biochemical Journal

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“…The mouse KOR gene is constitutively expressed in postnatal day 19 (P19) embryonal carcinoma stem cells; the level of KOR expression changes as cells undergo differentiation (Chen et al, 1999;. In addition to P19 carcinoma cells, various cancer cell lines also express KOR, including lung cancer (Maneckjee and Minna 1990;Kim et al, 1997), CNE2 human epithelial tumor (Diao et al, 2000), and human breast cancer (Hatzoglou et al, 1996).…”

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confidence: 99%

A Novel Signaling Pathway of Nitric Oxide on Transcriptional Regulation of Mouse κ Opioid Receptor Gene

Park

Loh

et al. 2002

J. Neurosci.

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Nitric oxide (NO) suppressed the transcription of the mouse kappa opioid receptor (KOR) gene, mediated by a rapid downregulation of c-myc gene expression. KOR was constitutively expressed in postnatal day 19 (P19) embryonal carcinoma stem cells and is suppressed by NO donors [sodium nitroprusside (SNP), 3-morpholinosydnonimine-1, and S-nitrosoglutathione] in P19 stem cells within 4 hr. The suppression was reversed by 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, an NO scavenger, but could not be blocked by dithiothreitol, ruling out S-nitrosylation as the underlying mechanism. The suppressive effect of NO on KOR occurred at the level of gene transcription, mediated by E boxes located in promoters I and II of this gene. Protein-DNA complexes that formed on these E boxes contained c-myc; c-myc expression was suppressed by NO in P19 stem cells within 2 hr of treatment. Furthermore, chromatin immunoprecipitation demonstrated reduced c-myc binding to the E boxes and hypoacetylation of histone H3 on the chromatin of endogenous KOR promoters in P19 stem cells treated with SNP. It is proposed that NO regulates KOR at the level of gene transcription, mediated by a rapid suppression of c-myc gene expression and its binding to KOR promoters, and followed by chromatin hypoacetylation of and reduced transcription from KOR promoters in P19 stem cells. A novel pathway mediating the potential interplay between NO and opioid systems is discussed.

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Hyponatremia: Clinical Diagnosis and Management

Lien¹,

Shapiro²

2007

The American Journal of Medicine

110

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Effect of κ opioid agonist RU 51599 on osmotic and non-osmotic stimulated arginine vasopressin release and gene regulation in small cell lung carcinoma cells

Cited by 3 publications

References 36 publications

E-box motifs within the human vasopressin gene promoter contribute to a major enhancer in small-cell lung cancer

E-box motifs within the human vasopressin gene promoter contribute to a major enhancer in small-cell lung cancer

A Novel Signaling Pathway of Nitric Oxide on Transcriptional Regulation of Mouse κ Opioid Receptor Gene

Hyponatremia: Clinical Diagnosis and Management

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