|Name||Mr. Israel Castillo Gonzalez|
|Organization or Institution||florida international university|
|Topic||Biochemistry / Chem Bio.|
Characterization of a mouse model of uveal melanoma.
Israel Castillo Gonzalez, Martina Cavallini, Lidia Kos
Florida International University
Uveal melanoma (UM) is the most common primary intraocular tumor found in adults. Mutations in the G protein subunit alpha q/11 (GNAQ/GNA11), which lead to the constitutive activation of the ERK1/2 pathway, drive the initiation and progression of UM. Approximately half of UM patients present with liver metastases several years after detection and treatment of the primary tumor and die within a short time. The transgenic mouse line Tg(Grm1) that expresses the metabotropic glutamate receptor 1 under the regulation of the melanocyte-specific dopachrome tautomerase promoter, has been proposed as a model for studying UM. Our colony of Tg(Grm1) mice start presenting with ocular lesions between 4 to 6 months after birth and cutaneous lesions in the ear and tail at around the same age. Our objective is to examine the expression of different cell signaling (ERK1/2, m-TOR, AKT), transcription factor (FOXP3) and EMT (E-cadherin, Vimentin) markers in our colony of TG(Grm1) mice. Histological analysis and H&E staining of transgenic eyes indicated the presence of thickened choroids that were invaded by large blood vessels in the posterior aspect, thickened iris that dislocated towards the cornea resulting in chamber angle closure, ciliary body atrophy and tumors with adjacent infiltration of the sclera by pigmented cells. Western blot analysis of transgenic eyes showed altered levels of Vimentin, FOXP3, p-ERK1/2, p-mTOR, and moderate levels of Gα but not pAKT and E-cadherin. These results confirm that our Tg(Grm1) mice can be used as a model that recapitulates the phenotype of GNAQ/GNA11 mutation and possibly of other variants and can potentially be used as a platform to test therapeutic avenues for this deadly form of eye cancer.