MP55-12 THE PROTON-ASSISTED AMINO ACID TRANSPORTER 4 (PAT4/SLC36A4) IS UP-REGULATED IN PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research III1 Apr 2015MP55-12 THE PROTON-ASSISTED AMINO ACID TRANSPORTER 4 (PAT4/SLC36A4) IS UP-REGULATED IN PROSTATE CANCER Daniel Stevens, Claire Verrill, Richard Bryant, Chad McKee, Helen Turley, Shih-Jung Fan, Sumeth Perera, Clive Wilson, Adrian L. Harris, Freddie C. Hamdy, and Deborah C.I. Goberdhan Daniel StevensDaniel Stevens More articles by this author , Claire VerrillClaire Verrill More articles by this author , Richard BryantRichard Bryant More articles by this author , Chad McKeeChad McKee More articles by this author , Helen TurleyHelen Turley More articles by this author , Shih-Jung FanShih-Jung Fan More articles by this author , Sumeth PereraSumeth Perera More articles by this author , Clive WilsonClive Wilson More articles by this author , Adrian L. HarrisAdrian L. Harris More articles by this author , Freddie C. HamdyFreddie C. Hamdy More articles by this author , and Deborah C.I. GoberdhanDeborah C.I. Goberdhan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2055AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Proton Assisted Amino Acid Transporter 4 (PAT4/SLC36A4) is expressed in many normal and cancer cells and is involved in amino acid-dependent activation of the mTORC1 pathway from the surface of intracellular compartments in several cancer types. However, its role in prostate cancer is unknown. Recent work has suggested that high levels of PAT4 play an important role in maintaining growth in colorectal cancer. METHODS Using a tissue microarray, immunohistochemistry was performed on formalin-fixed, paraffin-embedded prostate cancer samples and unmatched benign prostate tissue samples. A fully validated anti-PAT4 mouse monoclonal antibody was used to stain the tissue. Reporting was carried out by an expert Uro-Pathologist using the standardised immunoreactive score (IRS) system. Separate scores were produced for the presence of PAT4 in the cell cytoplasm and at the cell membrane. RESULTS 137 prostate cancer samples and 44 benign prostate tissue samples were stained for PAT4 expression. The mean cytoplasmic IRS was 2.41 (SEM 0.26) in benign tissue and 6.54 (SEM 0.33) in malignant tissue. The mean membrane IRS in benign tissue was 4.66 (SEM 0.47) and 3.26 (SEM 0.36) in malignant tissue. There is significantly more PAT4 at the plasma membrane in benign prostate tissue when compared to prostate cancer (p<0.02), and significantly more PAT4 in the cytoplasm of prostate cancer when compared to benign prostate tissue (p<0.001). CONCLUSIONS These data suggest for the first time that there is an up regulation of PAT4 and a significant shift from a predominantly membrane-bound to cytoplasmic localisation in malignant prostate cancer versus benign prostate tissue. In other cancer cell types, PAT4 at the surface of intracellular compartments stimulates mTORC1-dependent growth and high PAT4 levels make cells resistant to amino acid starvation. We are now analysing the roles of internalised PAT4 in prostate cancer cells. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e677 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Stevens More articles by this author Claire Verrill More articles by this author Richard Bryant More articles by this author Chad McKee More articles by this author Helen Turley More articles by this author Shih-Jung Fan More articles by this author Sumeth Perera More articles by this author Clive Wilson More articles by this author Adrian L. Harris More articles by this author Freddie C. Hamdy More articles by this author Deborah C.I. Goberdhan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...