60S acidic ribosomal protein P1 and endometriosis pathogenesis

University Of Kansas Medical Center, Kansas City KS

Investigators

Abstract

Project Summary Endometriosis is a significant disease which affects over 70 million women globally. Defined as ectopic growth of endometrial tissue (glands and stroma), this disease impacts the daily lives of young girls and women reducing their quality of life, impacting their education, and careers. Endometriosis treatment primarily relies on reduction of estrogen production and/or action. This treatment is not effective in all women, it is not well-tolerated and it is associated with unwanted and potentially health-compromising side effects. As such, there is a clear need for the identification of novel, estrogen-sparing treatments for this common, debilitating disease. Limitations in our ability to successfully treat endometriosis are hindered by our incomplete understanding on the pathogenesis of the disease. Beyond the fact the endometriosis is an estrogen-dependent disease the precise mediators of lesion survival, pain and infertility are largely unknown. In this application we report for the first time that the 60S acidic ribosomal protein P1 (RPLP1) is significantly over-expressed in endometriotic lesion tissue compared to eutopic endometrium from the same patient as well as from control subjects. RPLP1 plays an important role in protein synthesis and its over-expression has been detected in a variety of cancer cell types where it has been associated with cellular transformation, proliferation and invasion. We propose in this grant application to expand upon our initial findings and test the hypothesis that RPLP1 over-expression in human endometriotic lesion tissue enhances lesion survival. First, we will define the pattern and cellular localization of RPLP1 in endometriotic and paired endometrial tissue in a large, well characterized patient population demonstrating that RPLP1 over-expression is associated with viable/proliferating endometriotic lesion tissue. Secondly, we will use a novel approach/animal model for endometriosis to demonstrate the functional role of RPLP1 in lesion survival. Lastly, we will identify downstream targets of RPLP1 which may represent novel, non-hormonal targets for endometriosis treatment. The proposed research will provide new knowledge in field of endometriosis identifying a novel signaling pathways relevant to the pathogenesis of endometriosis. The long-term benefits of this research will enhance our understanding on the disease endometriosis and potentially improve women's health. The outcomes from the proposed research have the potential to change the way endometriosis may be treated and may offer new options.