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Metabotropic glutamate receptor 1 and glutamate signaling in human melanoma
Descriptive
TitleInfo
Title
Metabotropic glutamate receptor 1 and glutamate signaling in human melanoma
Name
(type = personal)
NamePart
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Namkoong
NamePart
(type = given)
Jin
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Jin Namkoong
Role
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author
Name
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(type = family)
Axelrod
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David
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Advisory Committee
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David E. Axelrod
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chair
Name
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NamePart
(type = family)
Chen
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Suzie
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Advisory Committee
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Suzie Chen
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internal member
Name
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(type = family)
Zhou
NamePart
(type = given)
Renping
Affiliation
Advisory Committee
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Renping Zhou
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(authority = RULIB)
internal member
Name
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(type = family)
Goydos
NamePart
(type = given)
James
Affiliation
Advisory Committee
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James S. Goydos
Role
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(authority = RULIB)
outside member
Name
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NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB)
degree grantor
Name
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NamePart
Graduate School-New Brunswick
Role
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school
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Text
Genre
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theses
OriginInfo
DateCreated
(qualifier = exact)
2007
DateOther
(qualifier = exact);
(type = degree)
2007
Language
LanguageTerm
(authority = ISO 639-3:2007);
(type = text)
English
PhysicalDescription
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electronic
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application/pdf
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text/xml
Extent
xiii, 135 pages
Abstract
(type = abstract)
Melanoma is the most malignant form of skin cancers that originated from melanocytes, the pigment cells in the skin. Early detection is the key for increased chance of survival, since currently there is no assuring therapeutic means for late stage melanoma. Animal models have been a valuable tool to understand human disorders and to identify new therapeutic targets for the treatments of a disease including melanoma. Previously, we reported on a transgenic mouse model with predisposition to melanoma development with 100% penetrance [37]. Subsequent studies identified the aberrant expression of metabotropic glutamate receptor 1 (Grm1) in melanocytes to be critical in the onset of melanoma. Confirmation of the etiological role of Grm1 in melanoma development was demonstrated in a second transgenic mouse line with Grm1 expression under the regulation of a melanocyte-specific dopachrome tautomerase (DCT) promoter [40].
Ectopic expression of GRM1 was also detected in a subset of human melanoma cell lines and biopsies, suggesting that aberrant expression of GRM1 in melanocytes may contribute to the development of human melanoma. GRM1, a seven-transmembrane domain G-protein coupled receptor, is normally expressed and functional in neuronal cells and its ligand, glutamate, is the major excitatory neurotransmitter. MAPK has been shown by many investigators to be one of the key signaling pathways in human melanoma cell proliferation [45, 55]; We also showed that MAPK signaling cascade being the downstream target of activated GRM1 [47]. Furthermore, treatment of GRM1- expressing human melanoma cells with a GRM1-antagonist leads to a suppression of cell proliferation. Human melanoma cells released elevated levels of glutamate, implying a possible autocrine loop. Treatment of human melanoma cells with a GRM1-antagonist or an inhibitor of glutamate release, Riluzole, leads to a decrease in release of glutamate and suppression of cell growth. In vivo xenografts with human melanoma cells, when treated with Riluzole, resulted in an inhibition of tumor growth/progression. Taken together, these data suggest the pivotal role of glutamate signaling in human melanoma and imply the potential of a new target for melanoma therapy.
Ectopic expression of GRM1 was also detected in a subset of human melanoma cell lines and biopsies, suggesting that aberrant expression of GRM1 in melanocytes may contribute to the development of human melanoma. GRM1, a seven-transmembrane domain G-protein coupled receptor, is normally expressed and functional in neuronal cells and its ligand, glutamate, is the major excitatory neurotransmitter. MAPK has been shown by many investigators to be one of the key signaling pathways in human melanoma cell proliferation [45, 55]; We also showed that MAPK signaling cascade being the downstream target of activated GRM1 [47]. Furthermore, treatment of GRM1- expressing human melanoma cells with a GRM1-antagonist leads to a suppression of cell proliferation. Human melanoma cells released elevated levels of glutamate, implying a possible autocrine loop. Treatment of human melanoma cells with a GRM1-antagonist or an inhibitor of glutamate release, Riluzole, leads to a decrease in release of glutamate and suppression of cell growth. In vivo xenografts with human melanoma cells, when treated with Riluzole, resulted in an inhibition of tumor growth/progression. Taken together, these data suggest the pivotal role of glutamate signaling in human melanoma and imply the potential of a new target for melanoma therapy.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references (p. 66-75).
Subject
(authority = RUETD)
Topic
Microbiology and Molecular Genetics
Subject
(authority = ETD-LCSH)
Topic
Melanoma
Subject
(authority = ETD-LCSH)
Topic
Cancer
Subject
(authority = ETD-LCSH)
Topic
Skin
RelatedItem
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
Identifier
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.13495
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ETD_130
Identifier
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doi:10.7282/T3M61KP4
Location
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
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ETD doctoral
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Rights
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The author owns the copyright to this work.
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Copyright protected
Availability
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Open
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Name
Jin Namkoong
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Copyright holder
Affiliation
Rutgers University. Graduate School-New Brunswick
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Non-exclusive ETD license
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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