The deduced amino acid sequence is characteristic of a zinc-finger transcription factor. We have now also cloned the human homologue of r Lot 1 and shown it to map to a frequent site of loss of heterozygosity, 6q25, in ovarian and breast cancer. Ongoing work with Lot 1 involves defining its functional role and genomic organization. We have also found that cathepsin B is frequently overexpressed in transformed rat ovarian surface epithelial cells, and are in the process of determining the mechanism of overexpression and relevance to clinical ovarian cancer. Using this method, we have identified 28 differentially expressed cDNAs.
Thorough characterization is ongoing.
Additionally, we are developing techniques to specifically transfer genes to the rat ovary as a prelude to developing a transgenic model of ovarian cancer. We are currently investigating several experimental therapies for ovarian cancer. We are evaluating agents that block angiogenesis based on accumulated data that angiogenesis is critical to tumor growth and metastasis. We are also evaluating a controlled release formulation of paclitaxel based on data that repeated intraperitoneal infusion of paclitaxel has efficacy in the treatment of drug resistant ovarian cancer. We recently discovered a preneoplastic phenotype in the ovaries of ovarian cancer-prone women.