Henshall Susan M, Afar Daniel E H, Rasiah Krishan K, Horvath Lisa G, Gish Kurt, Caras Ingrid, Ramakrishnan Vanitha, Wong Melanie, Jeffry Ursula, Kench James G, Quinn David I, Turner Jennifer J, Delprado Warick, Lee C-Soon, Golovsky David, Brenner Phillip C, O'Neill Gordon F, Kooner Raji, Stricker Phillip D, Grygiel John J, Mack David H, Sutherland Robert L
Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst NSW 2010, Australia.
Oncogene. 2003 Sep 4;22(38):6005-12. doi: 10.1038/sj.onc.1206797.
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.
我们利用寡核苷酸微阵列来鉴定前列腺癌中具有潜在临床和生物学重要性的新基因。使用定制的Affymetrix基因芯片寡核苷酸微阵列分析了来自74例前列腺癌和代表40种不同组织的164份正常身体样本的RNA，该微阵列代表了超过90%的人类表达基因组。锌转运蛋白ZnT4的基因是与其他器官的正常组织相比在前列腺癌中表达显著更高的几个基因之一。通过免疫组织化学，使用多克隆抗肽抗体在所有165个良性前列腺组织样本和326个局限性前列腺癌组织样本的上皮中以及10个晚期前列腺癌标本中的9个中证实了ZnT4的表达。有趣的是，从良性前列腺组织到侵袭性局限性前列腺癌再到转移性疾病的进展过程中，ZnT4免疫反应性强度降低。对表达ZnT4的细胞进行的免疫荧光分析和表面生物素化研究将该蛋白定位到细胞内囊泡和质膜。这些发现与ZnT4在锌向细胞膜的囊泡转运以及可能在前列腺中锌的外排中所起的作用一致。
