Changes of dopamine content and cell proliferation by dexamethsone via pituitary adenylate cyclase-activating polypeptide in PC12 cell

Yang, Ting; Tsao, Chiung Wen; Li, Jin Shiou; Wu, Hung Tsung; Hsu, Cheng‐Ting; Cheng, Juei Tang

doi:10.1016/j.neulet.2007.08.037

Cited by 10 publications

(5 citation statements)

References 22 publications

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“…Furthermore, dopamine secretion is increased in some cases of the rare malignancy, pheochromocytoma [32][33][34] and in carcinoid tumors, 35 although the consequences of this secretion on tumor growth or progression is unclear. However, agents such as dexamethasone that increase pheochromocytoma dopamine content also increase cell proliferation, 36 suggesting that there may be a causal link between increased dopamine content and cell proliferation in these tumor cells. Conversely, dopamine levels are depleted in malignant colon tissue 12 and gastric cancer tissues, 13 whereas dopamine treatment slows tumor growth, presumably by decreasing the expression of vascular epithelial growth factor and subsequent angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Increased local dopamine secretion has growth‐promoting effects in cholangiocarcinoma

Coufal

Invernizzi

Gaudio

et al. 2009

Intl Journal of Cancer

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Cholangiocarcinoma is a devastating cancer of biliary origin with limited treatment options. Symptoms are usually evident after blockage of the bile duct by the tumor, and at this late stage, they are relatively resistant to chemotherapy and radiation therapy. Therefore, it is imperative that alternative treatment options are explored. We have previously shown that serotonin metabolism is dysregulated in cholangiocarcinoma leading to an increased secretion of serotonin, which has growth-promoting effects. Because serotonin and dopamine share the degradation machinery, we evaluated the secretion of dopamine from cholangiocarcinoma and its effects on cell proliferation. Using 4 cholangiocarcinoma cell lines and human biopsy samples, we demonstrated that there was an increase in mRNA and protein expression of the dopamine synthesis enzymes tyrosine hydroxylase and dopa decarboxylase in cholangiocarcinoma. There was increased dopamine secretion from cholangiocarcinoma cell lines compared to H69 and HIBEC cholangiocytes and increased dopamine immunoreactivity in human biopsy samples. Furthermore, administration of dopamine to all cholangiocarcinoma cell lines studied increased proliferation by up to 30%, which could be blocked by the pretreatment of the D2 and D4 dopamine receptor antagonists, whereas blocking dopamine production by a-methyldopa administration suppressed growth by up to 25%. Administration of a-methyldopa to nude mice also suppressed cholangiocarcinoma tumor growth. The data presented here represent the first evidence that dopamine metabolism is dysregulated in cholangiocarcinoma and that modulation of dopamine synthesis may represent an alternative target for the development of therapeutic strategies.Cholangiocarcinoma arises from the neoplastic transformation of the epithelial cells or cholangiocytes that line the bile ducts. It accounts for about 3% of all gastrointestinal cancers and represent the second most common primary liver tumor after hepatocellular carcinoma.1 Biliary tumors are extremely aggressive and display a poor prognosis.1-4 The lack of therapeutic tools for such a devastating disease is due, at least in part, to the lack of knowledge regarding the mechanisms regulating cholangiocarcinoma growth. 2-4 However, increasing evidence has shown that neuropeptides and neuroendocrine hormones are amongst those factors that are able to affect cholangiocarcinoma biology, either promoting or inhibiting its growth. 1,[4][5][6][7] We recently demonstrated that cholangiocarcinoma overproduces and secretes serotonin, which has growth-promoting effects in an autocrine manner. 6 Specifically,

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Section: Discussionmentioning

confidence: 99%

Increased local dopamine secretion has growth‐promoting effects in cholangiocarcinoma

Coufal

Invernizzi

Gaudio

et al. 2009

Intl Journal of Cancer

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“…The promoter region of the human PACAP gene does not contain any apparent TATA or CAAT boxes, which are normally required for accurate initiation of transcription (Hampsey, 1998). Investigation of the promoter activity has revealed that PACAP is constitutively expressed and that transcription of the PACAP gene can be enhanced by cAMP, phorbol diester, thyroid-specific transcription factor-1, dexamethasone, progesterone, and even by PACAP itself Ha et al, 2000;Hashimoto et al, 2000b;Kim et al, 2002;Chi-Wei et al, 2007;Yang et al, 2007). The 5Ј-flanking region contains two neural-restrictive silencer-like elements 1 and 2, which might be involved in neuron-specific PACAP gene expression (Fig.…”

Section: The Pituitary Adenylate Cyclase-activating Polypeptide Genementioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

et al. 2009

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“…After 72 hours of culturing the cells MTT was added for 1 h. Following incubation with MTT (Sigma®) the cells were lysed with DMSO and the absorbance was measured at 570 nM using Tecan® spectrofluorometer. The percent of proliferation was calculated compared to untreated cultures [18].…”

Section: Measurement Of Cell Proliferationmentioning

confidence: 99%

Dexamethasone-Induced Down-Regulation of Nerve Growth Factor Receptor p75NTR is Mediated by Glucocorticoid Type II Receptor in PC12 Cell Model

Lecht¹,

Arien‐Zakay²,

Tabakman³

et al. 2007

TOPHARMJ

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PC12 clones are established neuronal models to investigate mechanisms involved in the cross-talk between the neurotrophins and drugs. Chronic treatment of PC12 cells with the glucocorticoid agonist drug, dexamethasone (Dex), elicited a 50% decrease in the selective binding of 125 I-NGF along with a reduction in the NGF receptor p75 NTR mRNA and protein levels, suggesting a transcriptional mechanism. This down regulation of p75 NTR was antagonized by the glucocorticoid type II receptor (GR-2), RU-38486 but not by the minerallocorticoid receptor, RU-28318, antagonists. This process was associated with increased autophosphorylation of the NGF receptor, TrkA. Chronic treatment of PC12 with Dex abolished the NGF-induced proliferation of the cells after 20 hours and inhibited by 45% the neurite elongation after 96 hours. RU-38486 blocked Dex-induced shift of PC12 cells from dopaminergic to noradrenergic phenotype. Dexinduced down regulation of p75 NTR receptor is mediated by GR-2 and is correlated with disruption of NGF induced proliferation and differentiation. This study may prove relevant with respect to the understanding of neuronal side-effects of corticosteroids.

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Changes of dopamine content and cell proliferation by dexamethsone via pituitary adenylate cyclase-activating polypeptide in PC12 cell

Cited by 10 publications

References 22 publications

Increased local dopamine secretion has growth‐promoting effects in cholangiocarcinoma

Increased local dopamine secretion has growth‐promoting effects in cholangiocarcinoma

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

Dexamethasone-Induced Down-Regulation of Nerve Growth Factor Receptor p75NTR is Mediated by Glucocorticoid Type II Receptor in PC12 Cell Model

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