Progesterone receptors in development and metatstais of endometrial cancer

Many women may acquire endometrial cancer during their life. The vast majority of these women will be cured because of early detection of the disease. As in most types of cancer however, the main cause of death lies in metastasis of the primary tumor to other sites in the body. In approximately 25% of endometrial cancer patients, the tumor has spread beyond the uterus at the time of initial surgical treatment. During endometrial carcinogenesis, the balance between estrogen and progesterone is of great importance. This is indicated by the fact that virtually all risk factors for endometrial cancer are linked to a surplus of estrogenic effects that are not balanced by appropriate progestagenic effects. Also during further development and progression of endometrial cancer, steroid receptor signaling has many important effects. The major research question of this thesis is summarized as follows: what is the effect of loss of progesterone regulation due to loss of PR expression during development of endometrial cancer? More specifically, the questions that this thesis addresses are: 1) Is loss of PR expression in endometrial cancer linked to development of endometrial cancer to a more advanced stage? 2) What are the effects of changes in expression of PRA and PRB on invasion and metastasis of endometrial cancer? 3) What is the effect of progesterone on invasion and metastasis of endometrial cancer cells that express different PR isotypes? 4) Does any crosstalk exist between PR signaling and Wnt signaling?