2004 Liz Tilberis Early Career Award Recipient — Oliver Dorigo, MD, PhD
Project Summary
Cancer cells grow due to a range of different mechanisms such as, the over-expression of oncogenes, or genes that cause cancer, or the shutdown of genes encoding tumor suppressors, or genes that stop cancerous growth. The PTEN gene encodes for a protein that suppresses cancer cell growth. Mutations of the PTEN tumor suppressor gene are seen in various malignancies, including brain, endometrial and ovarian cancer. Lack of PTEN results in the activation of a protein, called Akt, which then activates a variety of cell signals that lead to increased ovarian cancer cell growth. But in ovarian cancer cell cultures and animal experiments, inhibition of the Akt pathway, by over-expression of PTEN, results in significant slower tumor growth and cell death.
This project is designed to further elucidate the role of PTEN and the Akt pathways in ovarian cancer by studying Akt activity in the mouse ovary in an animal engineered to be missing the gene for PTEN. Based on previous observations in a prostate tumor model, Dr. Dorigo expects that activation of the Akt pathway in mouse ovarian tissue will result in significant molecular and cellular changes and possible ovarian tumor disease. He will also study changes in protein and gene expression using microarray technology, a method that allows the analysis of many genes simultaneously. The results from this study will provide insight into the Akt regulated signaling events in mouse ovary with the identification of possibly novel genes that are important in the pathogenesis of ovarian cancer.