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Using LNS8801, a GPER agonist, to treat GRM1+ melanoma in a transgenic mouse model
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Marinaro, Christina N.. Using LNS8801, a GPER agonist, to treat GRM1+ melanoma in a transgenic mouse model. Retrieved from https://doi.org/doi:10.7282/t3-gyrr-hs11

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TitleUsing LNS8801, a GPER agonist, to treat GRM1+ melanoma in a transgenic mouse model
NameMarinaro, Christina N. (author); Minden, Audrey (chair); Rutgers University; School of Graduate Studies
Date Created2020
Other Date2020-10 (degree)
SubjectCancer, Microbiology and Molecular Genetics
Extent1 online resource (viii, 63 pages) : illustrations
DescriptionMelanoma is the most aggressive form of skin cancer. The American Cancer Society estimated that over 100,000 new cases will be diagnosed and there will be over 7,000 deaths from the disease in 2020. There are several signaling pathways critical for the onset and progression of this deadly disease. The sex hormone, estrogen, has been shown to act directly on melanocytes through G-protein coupled estrogen receptors (GPER). This interaction results in increased pigmentation and differentiation in melanocytes to establish a protective effect against cellular transformation. The activation and subsequent signaling cascades associated with GPER are unique to melanocytes and do not overlap with the classical estrogen pathways. Linnaeus Therapeutics Inc. has identified and isolated a unique isomer, LNS8801 as the active component of the GPER agonist G-1. Previous studies with LNS8801 in melanoma allograft mouse models showed a reduction in tumor progression and a lasting protective activity upon secondary challenge of the same tumor cells.

Our lab was the first to show that ectopic expression of a normal neuronal receptor, metabotropic glutamate receptor 1 (mGluR1/GRM1) in melanocytes is sufficient to transform cells in vitro and induce tumors in vivo. We established two transgenic mouse models, TG-3 and TGS, with aberrant GRM1 expression that develop metastatic melanoma spontaneously with 100% penetrance. In this project we propose to use the unique TGS mouse model and treat the animals with LNS8801 over 32 weeks to see the consequences of activated GPER. Furthermore, to emulate exposure to the natural carcinogen, UV radiation, most people endure every day, we will expose mice to UV throughout the study. Possible alterations in disease progression will be monitored by a small animal imaging system (IVIS). Several key protein markers shown earlier to be involved in GPER signaling will be evaluated by Western blots in excised tumor tissue samples. Finally, cytokine analysis will also be performed to examine possible changes in levels of cytokines, two specific ones, interlukin-10 (IL-10) and interferon gamma (IFN-γ), shown in previous investigations.
NoteM.S.
NoteIncludes bibliographical references
Genretheses, ETD graduate
Persistent URLhttps://doi.org/doi:10.7282/t3-gyrr-hs11
LanguageEnglish
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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