Gastrin-Releasing Peptide Receptors Regulate Proliferation of C6 Glioma Cells through a Phosphatidylinositol 3-Kinase-Dependent Mechanism

Flores, Débora Gazzana; Farias, Caroline Brunetto de; Leites, Juliano; Oliveira, Marianne Schrader de; Lima, Rodrigo Cruz; Tamajusuku, Alessandra Sayuri Kikuchi; Leone, Luciane Pons Di; Meurer, Luíse; Brunetto, Algemir Lunardi; Schwartsmann, Gilberto; Lenz, Guido; Roesler, Rafaël

doi:10.2174/156720208784310240

Cited by 33 publications

(35 citation statements)

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“…Notably, in experiments examining cancer cell growth (27,30,31), as well as in other experimental models (32)(33)(34), GRPR agonists and antagonists often show drug-response patterns, in which intermediate doses have more pronounced biological, whereas higher doses have no or even contrary effects. Moreover, the lack of a significant effect of RC-3095 in the present study might be owed to its lower potency compared to RC-3940-II.…”

Section: Discussionmentioning

confidence: 99%

“…Amplification conditions consisted of 1 min at 95˚C followed by 35 cycles of denaturation at 94˚C for 30 sec, annealing at 59˚C for 30 sec, extension of primers at 72˚C for 45 sec, followed by a final extension at 72˚C for 10 min. The products of BDNF (362 bp), GRPR (190 bp) and β-actin (190 bp) were electrophoresed through 2% agarose gels, stained with ethidium bromide and visualized under ultraviolet illumination (17,26,27). Each experiment was performed twice using RNA isolated from two independent cell cultures.…”

Section: Reverse Transcription-polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

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Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells

Cornélio

Farias

Prusch

et al. 2012

Molecular and Clinical Oncology

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Abstract. Neuropeptide and neurotrophin receptors are increasingly important molecular targets in cancer. Scientific findings indicate that compounds blocking gastrin-releasing peptide receptors (GRPR) or tropomyosin receptor kinase (Trk) receptors are likely to have antiproliferative activities against cancer cells. The present study aimed to demonstrate that, in contrast to previous findings, GRPR activation reduces, whereas its blockade increases the viability of breast, ovarian and cervical cancer cell lines. However, consistent with previous studies, Trk inhibition was demonstrated to reduce the viability of these cells. MCF-7 (breast), OVCAR-3 (ovarian) and HeLa (cervical) human cancer cell lines were treated with GRP, the GRPR antagonists RC-3095 and RC-3940-II, brain-derived neurotrophic factor (BDNF) and the Trk antagonist K252α. Cell viability was measured by the MTT assay. Expression of GRPR and BDNF was confirmed with reverse transcription-polymerase chain reaction (RT-PCR). GRP reduced, whereas RC-3940-II enhanced the viability of the three cell lines. Treatment with K252α inhibited the viability of the cell lines, while BDNF increased the viability of OVCAR-3 cells. The results supported the hypothesis that GRPR and BDNF/TrkB signaling regulates cancer cell viability. Most importantly, these findings are the first to demonstrate that GRPR blockade can stimulate, rather than inhibits the viability of breast and gynecologic cancer cell lines.

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Section: Discussionmentioning

confidence: 99%

Section: Reverse Transcription-polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells

Cornélio

Farias

Prusch

et al. 2012

Molecular and Clinical Oncology

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“…Molecular and cell biology 1) Cell culture and in vitro treatments Human, rat, and mouse neural and cancer cell lines are grown and maintained as previously described. 30 Cultures are treated with agents that modulate membrane receptors, intracellular cell signaling pathways and epigenetic mechanisms. 30,31 2) Cell proliferation and viability assays Cell proliferation and viability are assessed by cell counting in a hemocytometer and the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay.…”

Section: -Strategies To Investigate Neurobehavioral Function and Cmentioning

confidence: 99%

“…30 Cultures are treated with agents that modulate membrane receptors, intracellular cell signaling pathways and epigenetic mechanisms. 30,31 2) Cell proliferation and viability assays Cell proliferation and viability are assessed by cell counting in a hemocytometer and the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. 30,31 3) Reverse transcriptase polymerase chain reaction (RT-PCR) The expression of mRNA for molecular targets in cultured cells is analyzed by RT-PCR using appropriate primers as previously described.…”

Section: -Strategies To Investigate Neurobehavioral Function and Cmentioning

confidence: 99%

“…30,31 2) Cell proliferation and viability assays Cell proliferation and viability are assessed by cell counting in a hemocytometer and the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. 30,31 3) Reverse transcriptase polymerase chain reaction (RT-PCR) The expression of mRNA for molecular targets in cultured cells is analyzed by RT-PCR using appropriate primers as previously described. 30,31 4) Immunohistochemistry The expression of proteins for molecular targets in cultured cells and biopsy samples from patients is examined by immunohistochemistry using appropriate antibodies as previously described.…”

Section: -Strategies To Investigate Neurobehavioral Function and Cmentioning

confidence: 99%

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Instituto Nacional de Ciência e Tecnologia em Medicina Translacional (INCT-TM): abordagens metodológicas

Hallak

Crippa

Quevedo

et al. 2010

Rev. Bras. Psiquiatr.

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Objective: Translational medicine has been described as the integrated application of innovative pharmacology tools, biomarkers, clinical methods, clinical technologies and study designs to improve the understanding of medical disorders. In medicine, translational research offers an opportunity for applying the findings obtained from basic research to every-day clinical applications. The National Science and Technology Institute for Translational Medicine is comprised of six member institutions (Universidade Federal do Rio Grande do Sul, Universidade de São Paulo-Ribeirão Preto, Universidade Federal do Rio de Janeiro, Pontifícia Universidade Católica do Rio Grande do Sul, Universidade Estadual de Santa Catarina and a core facility that serves all centers). The objectives of the project are divided into four areas: Institutional, Research, Human Resources and Technology for the Community and Productive Sector. Method: In this manuscript, we describe some of the approaches used to attain the main objectives of the National Science and Technology Institute for Translational Medicine, which include the development of 1) animal models for bipolar disorder; 2) strategies to investigate neurobehavioral function and cognitive dysfunction associated with brain disorders; 3) experimental models of brain function and behavior, neuropsychiatric disorders, cell proliferation, and cancer; 4) Simulated Public Speaking and 5) Virtual reality simulation for inducing panic disorder and agoraphobia. Conclusion: The main focus of the National Science and Technology Institute for Translational Medicine is the development of more useful methods that allow for a better application of basic research-based knowledge to the medical field. Descriptors

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Protective effect of RC-3095, an antagonist of the gastrin-releasing peptide receptor, in experimental arthritis

Oliveira¹,

Grespan²,

Pinto³

et al. 2011

Arthritis & Rheumatism

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Objective. To evaluate the antiinflammatory effects of RC-3095 in 2 experimental models of arthritis, collagen-induced arthritis (CIA) and antigen-induced arthritis (AIA), and to determine the mechanisms of action involved.Methods. RC-3095 was administered daily to mice with CIA and mice with AIA, after induction of disease with methylated bovine serum albumin. Disease incidence and severity were assessed using a clinical index and evaluation of histologic features, respectively. In mice with CIA, gastrin-releasing peptide receptor (GRPR) was detected by immunohistochemical analysis, while in mice with AIA, migration of neutrophils, presence of glycosaminoglycans, and lymphocyte proliferation, determined using the MTT assay, were assessed. Expression of cytokines interleukin-17 (IL-17), IL-1␤, and tumor necrosis factor ␣ (TNF␣) was evaluated in all mouse knees using enzyme-linked immunosorbent assay. Treg cell production was assessed by flow cytometry in the joints of mice with AIA.Results. In mice with AIA, administration of RC-3095 reduced neutrophil migration, mechanical hypernociception, and proteoglycan loss. These findings were associated with inhibition of the levels of all 3 proinflammatory cytokines, decreased lymphocyte proliferation, and increased Treg cell numbers. In the CIA model, treatment with RC-3095 led to a significant reduction in arthritis clinical scores and the severity of disease determined histologically. Synovial inflammation, synovial hyperplasia, pannus formation, and extensive erosive changes were all dramatically reduced in the arthritic mice treated with RC-3095. Furthermore, arthritic mice treated with RC-3095 showed a significant reduction in the concentrations of IL-17, IL-1␤, and TNF␣, and showed a diminished expression of GRPR.Conclusion. These findings suggest that the GRP pathway has a significant role in chronic arthritis, and its inhibition can be explored as a possible therapeutic strategy in rheumatoid arthritis.

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Gastrin-Releasing Peptide Receptors Regulate Proliferation of C6 Glioma Cells through a Phosphatidylinositol 3-Kinase-Dependent Mechanism

Cited by 33 publications

References 0 publications

Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells

Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells

Instituto Nacional de Ciência e Tecnologia em Medicina Translacional (INCT-TM): abordagens metodológicas

Protective effect of RC-3095, an antagonist of the gastrin-releasing peptide receptor, in experimental arthritis

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