Abstract 3260: Primary cilia are lost early in prostate cancer progression

Prostate cancer is the most prominently diagnosed cancer in men, aside from non-melanoma skin cancer, and the second leading cause of cancer related deaths in men in the U.S. Little is known about the role of primary cilia in prostate cancer progression, so our goal is to elucidate this role. Primary cilia are microtubule-based organelles present on many mammalian cell types and help the cell sense the extracellular environment. Various signaling pathways important in development involve primary cilia, such as the Hedgehog (Hh) and Wingless/Int (Wnt) pathways, and these pathways are known to be misregulated in prostate cancer. Dysfunction of primary cilia is the cause of numerous ciliopathies, such as polycystic kidney disease and Bardet-Biedl syndrome, and has been linked to cancers, like basal cell carcinoma and medulloblastoma. We hypothesize that primary cilia suppress prostate tumorigenesis, and cilia loss promotes prostate cancer by altering cell signaling pathways like Hh and canonical Wnt. To test this hypothesis, we looked in human prostate cancers at cilia, Hh and canonical Wnt signaling. Human prostate tissue from prostate cancer patients was stained for ciliary proteins (acetylated and gamma tubulin). The expressions of these proteins were analyzed using confocal microscopy and compared between adjacent normal, hyperplastic, prostatic intraepithelial neoplasia (PIN), malignant and perineural invasion areas of each patient's tissue. As a control, normal prostate tissue from bladder cancer patients who underwent prostatectomies as part of treatment was used. A marked decrease in the percentage of ciliated cells in cancer and PIN was observed compared to normal prostate tissue. Higher grade cancer (Gleason sum α7) also had fewer cilia than lower grade (Gleason sum = 6). We are currently investigating Hh and canonical Wnt signaling activity in serial sections of the tissue used to analyze primary cilia. The expressions of Beta-Catenin, a protein used to measure canonical Wnt signaling activity, and Gli1, a transcription factor used as a readout of Hh activity, are being analyzed based on expression levels and localization within the cell, and correlated to primary cilia data. Thus far, our results suggest a role of primary cilia in promoting prostate cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL.