Expression of dopamine receptors and transporter in neuroendocrine gastrointestinal tumor cells

Lemmer, K.; Ahnert‐Hilger, Gudrun; Höpfner, Michael; Hoegerle, Stefan; Faiss, S; Grabowski, Patricia; Jockers-Scherübl, Maria C.; Riecken, Ernst–Otto; Zeitz, Martin; Scherübl, Hans

doi:10.1016/s0024-3205(02)01703-4

Cited by 52 publications

(32 citation statements)

References 29 publications

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“…Ishibashi et al (1994) showed the ability of bromocriptine, a dopaminergic agonist, in inhibiting the growth of human SCLC cells, implanted as tumor xenograft in athymic nude mice, in a dose-dependent manner. In the human neuroendocrine pancreatic cell line BON some authors have demonstrated the expression of D 2 (de Bruin et al 2009a) and the effect of the D 2 receptor agonist drug quinpirole in decreasing intracellular cAMP levels (Lemmer et al 2002). Recent studies also demonstrated a significant inhibitory effect of cabergoline, a D 2 preferential compound, in inhibiting cell proliferation both in lung carcinoma and in prostate cancer cell lines, endogenously expressing the D 2 (Ferone et al 2005.…”

Section: Ss and Da Analogs Treatment In Endocrine Tumorsmentioning

confidence: 99%

“…The observation of the expression of D 2 in GEP NET cell lines (Lemmer et al 2002) Recently, Grossrubatscher et al demonstrated the presence of D 2 in well-differentiated NET of different sites and in normal islet cells by IHC. They found a high expression of D 2 receptors among the tumors examined (85%), being bronchial carcinoids, islet cell tumors, and the NET of the duodenum the tumors with the highest receptor protein expression (Grossrubatscher et al 2008).…”

Section: Dr Expression In Endocrine Tumorsmentioning

confidence: 99%

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The role of somatostatin and dopamine D2 receptors in endocrine tumors

Gatto¹,

Hofland²

2011

Endocrine-Related Cancer

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Somatostatin (SS) and dopamine (DA) receptors have been highlighted as two critical regulators in the negative control of hormonal secretion in a wide group of human endocrine tumors. Both families of receptors belong to the superfamily of G protein-coupled receptors and share a number of structural and functional characteristics. Because of the generally reported high expression of somatostatin receptors (SSTRs) in neuroendocrine tumors (NET), somatostatin analogs (SSA) have a pronounced role in the medical therapy for this class of tumors, especially pituitary adenomas and well-differentiated gastroenteropancreatic NET (GEP NET). Moreover, NET express not only SSTR but also frequently dopamine receptors (DRs), and DA agonists targeting the D 2 receptor (D 2 ) have been demonstrated to be effective in controlling hormone secretion and cell proliferation in in vivo and in vitro studies. The treatment with SSAs combined with DA agonists has already been demonstrated efficacious in a subgroup of patients with GH-secreting pituitary adenomas and few reported cases of carcinoids. The recent availability of new selective and universal SSA and DA agonists, as well as the chimeric SS/DA compounds, may shed new light on the potential role of SSTR and D 2 as combined targets for biotherapy in NET. This review provides an overview of the latest studies evaluating the expression of SSTR and DR in NET, focusing on their co-expression and the possible clinical implications of such co-expression. Moreover, the most recent insights in SSTR and D 2 pathophysiology and the future perspectives for treatment with SSA, DA agonists, and SS/DA chimeric compounds are discussed.

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Section: Ss and Da Analogs Treatment In Endocrine Tumorsmentioning

confidence: 99%

Section: Dr Expression In Endocrine Tumorsmentioning

confidence: 99%

The role of somatostatin and dopamine D2 receptors in endocrine tumors

Gatto¹,

Hofland²

2011

Endocrine-Related Cancer

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“…Total RNA was purified with the RNeasy Mini kit (Qiagen, Germantown, MD). For PCR, the following primers were used (for dopamine receptors, primers were used from Lemmer et al, 2002); CCR-4: sense 5Ј-GTGCAGTCCTGAAGGACTTCAAGCTC-CACCAG-3Ј, antisense 5Ј-GGCAAGGACCCTGACCTATGGGGTCA-TCAC-3Ј; FOXP3: sense 5Ј-CAGCTGCCTACAGTGCCCCTAG-3Ј, antisense 5Ј-CATTTGCCAGCAGTGGGTAG-3Ј.…”

Section: Inhibition Assay (Coculturing Of Teff With Tregmentioning

confidence: 99%

Dopamine, through the Extracellular Signal-Regulated Kinase Pathway, Downregulates CD4⁺CD25⁺Regulatory T-Cell Activity: Implications for Neurodegeneration

Kipnis¹,

Cardon²,

Avidan³

et al. 2004

J. Neurosci.

180

170

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Fighting off neuronal degeneration requires a well controlled T-cell response against self-antigens residing in sites of the CNS damage. The ability to evoke this response is normally suppressed by naturally occurring CD4 ϩ CD25ϩ regulatory T-cells (Treg). No physiological compound that controls Treg activity has yet been identified. Here, we show that dopamine, acting via type 1 dopamine receptors (found here to be preferentially expressed by Treg), reduces the suppressive activity and the adhesive and migratory abilities of Treg. Treg activity was correlated with activation of the ERK1/2 (extracellular signal-regulated kinase 1/2) signaling pathway. Systemic injection of dopamine or an agonist of its type 1 receptors significantly enhanced, via a T-cell-dependent mechanism, protection against neuronal death after CNS mechanical and biochemical injury. These findings shed light on the physiological mechanisms controlling Treg and might open the way to novel therapeutic strategies for downregulating Treg activity (e.g., in neuronal degeneration) or for strengthening it (in autoimmune diseases).

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“…Human pancreatic carcinoid BON cells (Ahnert-Hilger et al, 1996;Lemmer et al, 2002) were maintained in a 1 : 1 mixture of DMEM, and F12K medium containing 10% FCS (Biochrom, Berlin, Germany) and 1% L-glutamine. The human insulinoma cell line CM (Baroni et al, 1999), kindly provided by Professor P Pozzilli (University La Sapienza of Rome, Italy), was cultured in RPMI 1640 supplemented with 5% FCS (Biochrom) and 1% L-glutamine.…”

Section: Cell Linesmentioning

confidence: 99%

A novel approach in the treatment of neuroendocrine gastrointestinal tumours. Targeting the epidermal growth factor receptor by gefitinib (ZD1839)

et al. 2003

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Therapeutic options to inhibit the growth and spread of neuroendocrine (NE) gastrointestinal tumours are still limited. Since gefitinib (4-(3-chloro-4-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline), an inhibitor of epidermal growth factor receptorsensitive tyrosine kinase (EGFR-TK), had been shown to suppress potently the growth of various non-NE tumour entities, we studied the antineoplastic potency of gefitinib in NE gastrointestinal tumour cells. In human insulinoma (CM) cells, in human pancreatic carcinoid (BON) cells and in NE tumour cells of the gut (STC-1), gefitinib induced a time-and dose-dependent growth inhibition by almost 100%. The antiproliferative potency of gefitinib correlated with the proliferation rate of the tumour cells. So the IC 50 value of gefitinib was 4.770.6 mM in the fast-growing CM cells, still 16.870.4 mM in the moderate-growing BON cells, and up to 31.572.5 mM in the slow-growing STC-1 cells. Similarly, the induction of apoptosis and cell-cycle arrest by gefitinib differed according to growth characteristics: fast-growing CM cells displayed a strong G0/G1 arrest in response to gefitinib, while no significant cell-cycle alterations were seen in the slow-growing STC-1. Vice versa, the proapoptotic effects of gefitinib, as determined by caspase-3 activation and DNA fragmentation, were most pronounced in the slow-growing STC-1 cells. Using cDNA microarrays, we found extensive changes in the expression of genes involved in the regulation of apoptosis and cell cycle after incubation with gefitinib. Among them, an upregulation of the growth arrest and DNA damage-inducible gene GADD153 was observed. Phosphorylation of ERK1/2, which inhibits GADD153 expression, was reduced in a time-dependent manner. However, no gefitinib-induced activation of the GADD153-inducing p38 mitogen-activated protein kinase was detected. Our data demonstrate that the inhibition of EGFR-TK by gefitinib induces growth inhibition, apoptosis and cell-cycle arrest in NE gastrointestinal tumour cells. Thus, EGFR-TK inhibition appears to be a promising novel approach for the treatment of NE tumour disease.

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Expression of dopamine receptors and transporter in neuroendocrine gastrointestinal tumor cells

Cited by 52 publications

References 29 publications

The role of somatostatin and dopamine D2 receptors in endocrine tumors

The role of somatostatin and dopamine D2 receptors in endocrine tumors

Dopamine, through the Extracellular Signal-Regulated Kinase Pathway, Downregulates CD4⁺CD25⁺Regulatory T-Cell Activity: Implications for Neurodegeneration

A novel approach in the treatment of neuroendocrine gastrointestinal tumours. Targeting the epidermal growth factor receptor by gefitinib (ZD1839)

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Expression of dopamine receptors and transporter in neuroendocrine gastrointestinal tumor cells

Cited by 52 publications

References 29 publications

The role of somatostatin and dopamine D2 receptors in endocrine tumors

The role of somatostatin and dopamine D2 receptors in endocrine tumors

Dopamine, through the Extracellular Signal-Regulated Kinase Pathway, Downregulates CD4+CD25+Regulatory T-Cell Activity: Implications for Neurodegeneration

A novel approach in the treatment of neuroendocrine gastrointestinal tumours. Targeting the epidermal growth factor receptor by gefitinib (ZD1839)

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Dopamine, through the Extracellular Signal-Regulated Kinase Pathway, Downregulates CD4⁺CD25⁺Regulatory T-Cell Activity: Implications for Neurodegeneration