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

Oncogene volume 22, pages 6005–6012 (2003)Cite this article

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.

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Abbreviations

BPH:

benign prostatic hyperplasia

HA:

hemagglutinin

IHC:

immunohistochemistry

kDa:

kilodalton

LNM:

lymph node metastases

MFC:

mouse fibroblast cells

NCBI:

National Center for Biotechnology Information

NBA:

normal body atlas

PIN:

prostatic intraepithelial neoplasia

SDS:

sodium dodecyl-sulfate

RP:

radical prostatectomy

References

  • Bubendorf L, Kolmer M, Kononen J, Koivisto P, Mousses S, Chen Y, Mahlamaki E, Schraml P, Moch H, Willi N, Elkahloun AG, Pretlow TG, Gasser TC, Mihatsch MJ, Sauter G and Kallioniemi O-P . (1999). J. Natl. Cancer Inst., 91, 1758–1761.

  • Carpten J, Nupponen N, Isaacs S, Sood R, Robbins C, Xu J, Faruque M, Moses T, Ewing C, Gillanders E, Hu P, Bujnovszky P, Makalowska I, Baffoe-Bonnie A, Faith D, Smith J, Stephan D, Wiley K, Brownstein M, Gildea D, Kelly B, Jenkins R, Hostetter G, Matikainen M, Schleutker J, Klinger K, Connors T, Xiang Y, Wang Z, De Marzo A, Papadopoulos N, Kallioniemi OP, Burk R, Meyers D, Gronberg H, Meltzer P, Silverman R, Bailey-Wilson J, Walsh P, Isaacs W and Trent J . (2002). Nat. Genet., 30, 181–184.

  • Cho Y-H, Lee S-J, Lee JY, Kim SW, Lee CB, Lee WY and Yoon MS . (2002). Int. J. Antimicrob. Agents, 19, 576–582.

  • Costello LC, Liu Y, Zou J and Franklin RB . (1999). J. Biol. Chem., 274, 17499–17504.

  • Costello LC, Liu YY, Franklin RB and Kennedy MC . (1997). J. Biol. Chem., 272, 28875–28881.

  • Dhanasekaran SM, Barrette TR, Ghosh D, Shah R, Varambally S, Kurachi K, Pienta KJ, Rubin MA and Chinnaiyan AM . (2001). Nature, 412, 822–826.

  • Feng P, Liang JY, Li TL, Guan ZX, Zou J and Franklin R . (2000). Mol. Urol., 4, 31–36.

  • Gleason D and Mellinger G . (1974). J. Urol., 111, 58–64.

  • Huang L and Gitshier J . (1997). Nat. Genet., 17, 292–297.

  • Huang L, Kirschke CP and Gitschier J . (2002). J. Biol. Chem., 277, 26389–26395.

  • Inoue K, Matsuda K, Itoh M, Kawaguchi H, Tomoike H, Aoyagi T, Nagai R, Hori M, Makamura Y and Tanaka T . (2002). Hum. Mol. Genet., 11, 1775–1784.

  • Kambe T, Narita H, Yamaguchi-Iwai Y, Hirose J, Amano T, Sugiura N, Sasaki R, Mori K, Iwanaga T and Nagao M . (2002). J. Biol. Chem., 277, 19049–19055.

  • Kononen J, Bubendorf L, Kallioniemi A, Bårlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G and Kallioniemi O-P . (1998). Nat. Med., 4, 844–847.

  • Liang JY, Liu YY, Zou J, Franklin RB, Costello LC and Feng P . (1999). Prostate, 40, 200–207.

  • McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D and Dallaire BK . (1998). J. Clin. Oncol., 16, 2825–2833.

  • McMahon RJ and Cousins RJ . (1998). J. Nutr., 128.

  • McNeal JE . (1997). Histology for Pathologists. Sternberg SS (ed). Lippincott-Raven Publishers: Philadelphia.

    Google Scholar 

  • Michalczyk AA, Allen J, Blomeley RC and Ackland ML . (2002). Biochem. J., 364, 105–113.

  • Murgia C, Vespignani I, Cerase J, Nobili F and Perozzi G . (1999). Am. J. Physiol., G1231–G1239.

  • Palmiter RD, Cole TB and Findley SD . (1996a). EMBO. J., 15, 1784–1791.

  • Palmiter RD, Cole TB, Quaife CJ and Findley SD . (1996b). Proc. Natl. Acad. Sci. USA, 93, 14934–14939.

  • Palmiter RD and Findley SD . (1995). EMBO. J., 14, 639–649.

  • Quinn DI, Henshall SM, Haynes A-M, Brenner PC, Kooner R, Golovsky D, Mathews J, O'Neil GF, Turner JJ, Delprado W, Finlayson JF, Sutherland RL, Grygiel JJ and Strieker PD . (2001). J. Clin. Oncol., 19, 3692–3705.

  • Singh D, Febbo PG, Ross K, Jackson DG, Manola J, Ladd C, Tamayo P, Renshaw AA, D’Amico AV, Richie JP, Lander ES, Loda M, Kantoff PW, Golub TR and Sellers WR . (2002). Cancer Cell., 1, 203–209.

  • Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J and Norton L . (2001). N. Engl. J. Med., 344, 783–792.

  • Uzzo RG, Leavis P, Hatch W, Gabai VL, Dulin N, Zvartau N and Kolenko VM . (2002). Clin. Cancer. Res., 8, 3579–3583.

  • Xu J, Zheng S, Komiya A, Mychaleckyj JC, Isaacs S, Hu J, Sterling D, Lange E, Hawkins G, Turner A, Ewing C, Faith D, Johnson J, Suzuki H, Bujnovszky P, Wiley K, DeMarzo A, Bova G, Chang B, Hall M, McCullough D, Partin A, Kassabian V, Carpten J, Bailey-Wilson J, Trent J, Ohar J, Bleecker E, Walsh P, Isaacs W and Meyers D . (2002). Nat. Genet., 32, 321–325.

  • Zaichick VY, Sviridova TV and Zaichick SV . (1997). Int. Urol. Nephrol., 29, 565–574.

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Acknowledgements

We thank Sr Anne-Maree Haynes, Luis Winoto and Catherine Langusch for their contributions to the management of the St Vincent's Campus Prostate Cancer Group Tissue Bank and Clinical database and Darren Head for expert technical assistance.

Author information

Author notes

  1. Daniel E H Afar, Kurt Gish, Vanitha Ramakrishnan, Melanie Wong & Ursula Jeffry

    Present address: Protein Design Lab. Inc., Fremont, CA, 94555, USA

Authors and Affiliations

  1. Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst, NSW 2010, Australia

    Susan M Henshall, Krishan K Rasiah, Lisa G Horvath, James G Kench, David I Quinn & Robert L Sutherland

  2. Genomics Research, Eos Biotechnology, South San Francisco, 94080, CA, USA

    Daniel E H Afar, Kurt Gish, Ingrid Caras, Vanitha Ramakrishnan, Melanie Wong, Ursula Jeffry & David H Mack

  3. Department of Anatomical Pathology, St Vincent's Hospital, Darlinghurst, NSW 2010, Australia

    Jennifer J Turner

  4. Douglass Hanly Moir Pathology, North Ryde NSW 2113, Australia

    Warick Delprado

  5. Department of Anatomical Pathology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia

    C-Soon Lee

  6. Department of Pathology, University of Sydney, Camperdown, NSW 2050, Australia

    C-Soon Lee

  7. Department of Urology, St Vincent's Hospital, Darlinghurst, NSW 2010, Australia

    David Golovsky, Phillip C Brenner, Gordon F O'Neill, Raji Kooner & Phillip D Stricker

  8. Department of Medical Oncology, St Vincent's Hospital, Darlinghurst, NSW 2010, Australia

    John J Grygiel

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  1. Susan M Henshall
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Corresponding author

Correspondence to Robert L Sutherland.

Additional information

This research was supported by grants from the National Health and Medical Research Council of Australia, The Cancer Council New South Wales, the RT Hall Trust, Freedman Foundation, Ronald Geoffrey Arnott Foundation, Australasian College of Surgeons, Australasian Urological Foundation, Prostate Cancer Foundation of Australia and the David Wilson Trust.

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Henshall, S., Afar, D., Rasiah, K. et al. Expression of the zinc transporter ZnT4 is decreased in the progression from early prostate disease to invasive prostate cancer. Oncogene 22, 6005–6012 (2003). https://doi.org/10.1038/sj.onc.1206797

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