MP39-10 EXOSOME-MEDIATED REGULATION OF PTEN EXPRESSION IN BLADDER CANCER

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You have accessJournal of UrologyBladder Cancer: Basic Research IV1 Apr 2014MP39-10 EXOSOME-MEDIATED REGULATION OF PTEN EXPRESSION IN BLADDER CANCER Adam Van Huis, Carrie Franzen, Kimberly Foreman, and Gopal Gupta Adam Van HuisAdam Van Huis More articles by this author , Carrie FranzenCarrie Franzen More articles by this author , Kimberly ForemanKimberly Foreman More articles by this author , and Gopal GuptaGopal Gupta More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1325AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Exosomes contain proteins, mRNA, and miRNA, thus potentially modulating signaling pathways in recipient cells. PTEN is a tumor suppressor protein which, when functional, inhibits the phosphoinositide-3-kinase (PI3-K) pathway. Inhibition of PI3-K leads to increased phospho-AKT and decreased proliferation. However, in many invasive forms of bladder cancer, PTEN expression is altered or deleted. METHODS Exosomes were isolated from PTEN-expressing bladder cancer cell lines (HT1376 or RT4 cells) by ultracentrifugation. Western blotting confirmed the presence of PTEN in the exosomes isolated from HT1376 and RT4 cells. These exosomes were then added to PTEN-null bladder cancer cells (UMUC3 or SW780 cells). Western blots were done on whole cell extracts to detect levels of phosphorylated AKT. To assess effects on cell proliferation, an MTT assay was performed on SW780 or UMUC3 cells incubated with HT1376 or RT4 exosomes. RESULTS In this study, we found that PTEN expressing bladder cancer cells can package PTEN into their secreted exosomes. In contrast, we verified that the SW780 and UMUC3 cell line did not express PTEN or packages it into their exosomes. Next, we found that treating SW780 or UMUC3 cells with exosomes from PTEN expressing cells decreased the levels of phosphorylated AKT. Furthermore, we showed that transfer of PTEN reduced the proliferation of SW780 and UMUC3 cells. CONCLUSIONS These data suggest that PTEN transfer via exosomes may play a role in altering the PI3-K pathway in bladder cancer cells, ultimately leading to a decrease in cellular proliferation. This study demonstrates that restoring PTEN in bladder cancer could be therapeutically beneficial by slowing proliferation and the progression in patients whose cancer show alterations to PTEN expression. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e429 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Adam Van Huis More articles by this author Carrie Franzen More articles by this author Kimberly Foreman More articles by this author Gopal Gupta More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...