Date of Award

12-1-2012

Degree Name

Master of Science

Department

Molecular Cellular and Systemic Physiology

First Advisor

Ellsworth, Buffy

Abstract

FOXO1 is a forkhead transcription factor that inhibits proliferation and promotes apoptosis. It regulates genes that are involved in many diverse processes, including regulation of cell proliferation and cancer. The goal of our research is to understand FOXO1 and the role that it plays in human pituitary adenomas. Three objectives were outlined in this project to help determine the expression of FOXO1 in human pituitary adenomas. The first objective of this project was to analyze the spatial and temporal pattern of FOXO1 during mouse pituitary development. Objective one results showed that starting at e12.5, FOXO1 is cytoplasmic and becomes more nuclear later on in development. Immunohistochemical co-staining of FOXO1 and bromodeoxyuridine (BrdU) showed that FOXO1 does not co-localize with BrdU at e12.5, e14.5, and e16.5 showing that FOXO1 is not expressed in actively proliferating cells. The goal of objective two was to determine if expression levels of FOXO1 were abnormal in human pituitary adenomas. The results of objective two showed that when compared to FOXO1 expression in human normal pituitaries, FOXO1 was decreased in gonodotropinomas, null cell adenomas, and prolactinomas. In corticotropinomas, FOXO1 expression was increased while in somatotropinomas, FOXO1 expression was the same as compared in human normal pituitaries. Objective three was to assess whether spatial distribution of FOXO1 protein is abnormal in human pituitary tumor tissue. Our data showed that statistically there is no difference in FOXO1 spatial distribution between pituitary and normal samples. Overall, our real time RT-PCR data showed that FOXO1 expression is reduced in human gonadotropinomas, null cell adenomas, and prolactinomas. FOXO1 expression was increased in human cortiocotropinomas while it remained the same in human somatotropinomas. Immunohistochemistry staining revealed that statistically there was no difference in FOXO1 expression in the human pituitary samples when compared to human normal pituitary samples. These findings lead to the idea that loss of FOXO1 may help contribute to human pituitary tumorigenesis but more than likely other factors are involved.

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