The ovary is a complex organ consisting of several different types of cells, including epithelial cells that cover the surface of the ovary, granulosa cells that surround the egg cells, and stromal cells or fibroblasts that provide support for the structure of the whole ovary. The most common type of ovarian cancer arises in the epithelial cells as a result of alterations in genes involved in cellular growth, control of cellular growth, and/or control of genetic integrity. Recent experimental evidence suggests that in addition to alterations of important genes in the epithelial cells themselves, alterations of genes in other cell types of the ovary, such as the granulosa cells and fibroblasts, may play an important role in ovarian cancer development. To try to study this in the laboratory, we propose to develop a new cell culture model system by isolating individual ovarian cell types (epithelial, granulose, and fibroblast cells) from mice that have mutant versions of either the BRCA1 or p53 gene or in both BRCA1 and p53 genes (BRCA1 and p53 are genes that are commonly mutated in inherited ovarian cancer). Individual ovarian cell types containing normal or mutant BRCA1 and/or p53 will then be grown together in different combinations in both two- and three-dimensional cell cultures to determine if mutations in granulosa cells or fibroblasts have an effect on growth (e.g., faster growth) of epithelial cells containing similar mutations. |
