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TitleContinuous expression of metabotropic glutamate receptor 1 is required for maintenance of tumorigenesis in GRM1 transformed mouse kidney epithelial cells
NameWilimczyk, Barbara J. (author), Chen, Suzie (chair), Ganesan, Shirdar (internal member), Axelrod, David (internal member), Rutgers University, Graduate School - New Brunswick,
Degree Date2009-05
Date Created2009
SubjectMicrobiology and Molecular Genetics,
Cancer cells--Proliferation,
Carcinogenesis,
Cancer--Treatment
DescriptionWithin the United States, skin cancer has become a predominant form of cancer that occurs across all age groups, racial backgrounds, and to both genders equally. Melanoma arises from malignant melanocytes that reside within the epidermis of the skin. It is the most serious form of skin cancer, causing the most mortality among all skin cancers. Currently, due to the limited treatment options available, patients have severely reduced survival rates as the disease advances toward Stage IV. Advancements in understanding of the mechanisms of melanoma development and novel targets for treatment are in great need for patients inflicted with this devastating disease.
Metabotropic glutamate receptors are normally expressed within the central nervous system (CNS) where they use glutamate, the most abundant neural transmitter, as their natural ligand. Within the CNS, these receptors have important diversified functions ranging from mediation of slow excitatory and inhibitory responses to memory formation and neuronal development. Our lab has identified the etiological role of Metabotropic Glutamate Receptor 1 (Grm1) in melanoma development in transgene mouse models. Subsequently, our lab also detected GRM1 expression in approximately 40% of human melanomas biopsy and cell line samples. These results led us to investigate the role of GRM1 in other types of cancer.
Epithelial cancers are the abundant category of cancers to inflict humans, relating GRM1 and its possible role in solid tumors could introduce a novel target for developing cancer therapies. Since continuous expression of Grm1 was demonstrated to be required for the maintenance of the tumorigenic phenotype in Grm1-mouse melanocytes, my project is to determine whether this is true for an epithelial cell system. With the use of Grm1-transformed mouse kidney epithelial cells, an inducible tetracycline siRNA system was introduced into the cells and tested with/without the inducer, doxycycline, for the suppression of Grm1 expression levels in vitro and in vivo. The in vivo data demonstrated decreased tumor volumes in the doxycycline treatment groups, validating the decreased expression of Grm1 seen in vitro, compared to the no treatment groups. These results provide evidence that Grm1 expression is necessary to maintain the tumorigenic phenotype of Grm1 transformed cells.
Metabotropic glutamate receptors are normally expressed within the central nervous system (CNS) where they use glutamate, the most abundant neural transmitter, as their natural ligand. Within the CNS, these receptors have important diversified functions ranging from mediation of slow excitatory and inhibitory responses to memory formation and neuronal development. Our lab has identified the etiological role of Metabotropic Glutamate Receptor 1 (Grm1) in melanoma development in transgene mouse models. Subsequently, our lab also detected GRM1 expression in approximately 40% of human melanomas biopsy and cell line samples. These results led us to investigate the role of GRM1 in other types of cancer.
Epithelial cancers are the abundant category of cancers to inflict humans, relating GRM1 and its possible role in solid tumors could introduce a novel target for developing cancer therapies. Since continuous expression of Grm1 was demonstrated to be required for the maintenance of the tumorigenic phenotype in Grm1-mouse melanocytes, my project is to determine whether this is true for an epithelial cell system. With the use of Grm1-transformed mouse kidney epithelial cells, an inducible tetracycline siRNA system was introduced into the cells and tested with/without the inducer, doxycycline, for the suppression of Grm1 expression levels in vitro and in vivo. The in vivo data demonstrated decreased tumor volumes in the doxycycline treatment groups, validating the decreased expression of Grm1 seen in vitro, compared to the no treatment groups. These results provide evidence that Grm1 expression is necessary to maintain the tumorigenic phenotype of Grm1 transformed cells.
NoteM.S.
NoteIncludes bibliographical references (p. 46-53)
Noteby Barbara J. Wilimczyk
Genretheses
Persistent URLhttp://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000051419
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.