Progesterone receptors in development and metatstais of endometrial cancer

Many women may acquire endometrial cancer during their life. The vast majority of \nthese women will be cured because of early detection of the disease. As in most \ntypes of cancer however, the main cause of death lies in metastasis of the primary \ntumor to other sites in the body. In approximately 25% of endometrial cancer \npatients, the tumor has spread beyond the uterus at the time of initial surgical \ntreatment. \nDuring endometrial carcinogenesis, the balance between estrogen and \nprogesterone is of great importance. This is indicated by the fact that virtually all risk \nfactors for endometrial cancer are linked to a surplus of estrogenic effects that are \nnot balanced by appropriate progestagenic effects. Also during further development \nand progression of endometrial cancer, steroid receptor signaling has many \nimportant effects. \nThe major research question of this thesis is summarized as follows: what is the \neffect of loss of progesterone regulation due to loss of PR expression during \ndevelopment of endometrial cancer? More specifically, the questions that this thesis \naddresses are: \n1) Is loss of PR expression in endometrial cancer linked to development of \nendometrial cancer to a more advanced stage? \n2) What are the effects of changes in expression of PRA and PRB on invasion \nand metastasis of endometrial cancer? \n3) What is the effect of progesterone on invasion and metastasis of endometrial \ncancer cells that express different PR isotypes? \n4) Does any crosstalk exist between PR signaling and Wnt signaling?