Characterization of spontaneous, juvenile-type granulosa cell tumours from SWR mice

Lewis, Clare (2018) Characterization of spontaneous, juvenile-type granulosa cell tumours from SWR mice. Masters thesis, Memorial University of Newfoundland.

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Abstract

Granulosa cell tumours (GCTs) are a subtype of ovarian cancer derived from the granulosa cells (GC) surrounding the oocytes. The SWR mouse is a well defined model for juvenile-type GCTs in terms of endocrinology, genetics and malignancy. GCTs appear spontaneously in SWR-derived female mice at puberty, characterized by rapid, benign growth followed by a malignant transition after 6-10 months in approximately half of the tumour-bearing population. Our aim is to characterize the protein expression profile of early GCTs, normal ovaries and the human COV434 JGCT cell line to determine if protein expression differences can help identify the mechanism of tumourigenesis. This was accomplished using immunoblotting to define the protein expression profile of mouse primary GCTs, normal, whole ovaries and human COV434 cell lysates. Protein lysates from the early GCTs were positive for expression of Cyp19a, Fshr, Egfr, Esr2, Foxl2 and Sox9 proteins, with significant downregulation of Esr2 and significant upregulation of Egfr in GCTs relative to both normal ovaries. A further evaluation of Sox9 was done by immunohistochemistry, which confirmed a proportion of cell specifically express Sox9, although the cellular identity is not conclusively that of GCT cells. Protein lysates from the COV434 cell line compared to the mouse GCTs were also positive for expression of Cyp19a, Fshr, Egfr, Esr2 and Foxl2 proteins, with significant upregulation of Cyp19a, significant downregulation of Egfr and Esr2, and no Sox9 protein expression. A further evaluation of Sox9 was done by immunohistochemistry and confirmed its expression in GCTs. The protein profile of GCTs, as compared to normal ovaries and a human representative cell line will provide a basis for future studies of juvenile-type GCT genetics, biology and therapy.

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