Expression of the zinc transporter ZnT4 is decreased in the progression from early prostate disease to invasive prostate cancer

Susan M. Henshall, Daniel E.H. Afar, Krishan K. Rasiah, Lisa G. Horvath, Kurt Gish, Ingrid Caras, Vanitha Ramakrishnan, Melanie Wong, Ursula Jeffry, James G. Kench, David I. Quinn, Jennifer J. Turner, Warick Delprado, C. Soon Lee, David Golovsky, Phillip C. Brenner, Gordon F. O'Neill, Raji Kooner, Phillip D. Stricker, John J. GrygielDavid H. Mack, Robert L. Sutherland*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)

Abstract

We have utilized oligonucleotide microarrays to identify novel genes of potential clinical and biological importance in prostate cancer. RNA from 74 prostate cancers and 164 normal body samples representing 40 different tissues were analysed using a customized Affymetrix GeneChip® oligonucleotide microarray representative of over 90% of the expressed human genome. The gene for the zinc transporter ZnT4 was one of several genes that displayed significantly higher expression in prostate cancer compared to normal tissues from other organs. A polyclonal antipeptide antibody was used to demonstrate ZnT4 expression in the epithelium of all 165 elements of benign and 326 elements of localized prostate cancers examined and in nine of 10 advanced prostate cancer specimens by immunohistochemistry. Interestingly, decreased intensity of ZnT4 immunoreactivity occurred in the progression from benign to invasive localized prostate cancer and to metastatic disease. Immunofluorescence analysis and surface biotinylation studies of cells expressing ZnT4 localised the protein to intracellular vesicles and to the plasma membrane. These findings are consistent with a role for ZnT4 in vesicular transport of zinc to the cell membrane and potentially in efflux of zinc in the prostate.

Original languageEnglish
Pages (from-to)6005-6012
Number of pages8
JournalOncogene
Volume22
Issue number38
DOIs
Publication statusPublished - 4 Sep 2003
Externally publishedYes

Keywords

  • Hyperplasia
  • Oligonucleotide microarrray
  • Prostate cancer
  • Zinc transporter
  • ZnT4

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