Androgen Effects in Ovarian Epithelial Cells and Cancer Predisposition

The main objective of this thesis is to further explore the role of androgen in initiation/progression of ovarian cancer and to uncover the underlying mecahnisms. Gene expression profiling by cDNA microarrays was initiated to explore the global effect of androgen on gene expression profiles of these cultures. The results demonstrate that ovarian epithelial cells respond to androgen by up-regulating hundreds of genes. The analysis of microarray data was combined with the information derived from known/predicted protein interactions in the form of networks defining the pathways of cellular functions. It was hypothesized that the androgen inhibitory effect on TGF-¿ inhibition in ovarian cancer may be mediated by this gene. High levels of cytoplasmic ACHE staining correlated with decreased survival, whereas nuclear BACH2 staining correlated with decreased time to disease recurrence. This finding supports a potential role for altered androgen effects in ovarian cancer initiation/progression. In addition to BACH2 and ACHE, this study highlights a set of potentially functionally related genes for further investigation in ovarian cancer.