Expression of the zinc transporter ZnT4 is decreased in the progression from early prostate disease to invasive prostate cancer.
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.
Henshall
Susan M
SM
Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst NSW 2010, Australia.
Afar
Daniel E H
DE
Rasiah
Krishan K
KK
Horvath
Lisa G
LG
Gish
Kurt
K
Caras
Ingrid
I
Ramakrishnan
Vanitha
V
Wong
Melanie
M
Jeffry
Ursula
U
Kench
James G
JG
Quinn
David I
DI
Turner
Jennifer J
JJ
Delprado
Warick
W
Lee
C-Soon
CS
Golovsky
David
D
Brenner
Phillip C
PC
O'Neill
Gordon F
GF
Kooner
Raji
R
Stricker
Phillip D
PD
Grygiel
John J
JJ
Mack
David H
DH
Sutherland
Robert L
RL
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D027682:Cation Transport Proteins; D002462:Cell Membrane / Q000378:metabolism; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011467:Prostate / Q000502:physiology; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012016:Reference Values; D022161:Transport Vesicles / Q000378:metabolism
D002352:Carrier Proteins; D027682:Cation Transport Proteins; C491597:SLC30A4 protein, human