Aberrant expression of zinc transporter ZIP4 (SLC39A4) significantly contributes to human pancreatic cancer pathogenesis and progression

• DOI: 10.1073/pnas.0709307104
• Publication Date: 2007-11-15T02:19:01Z
• Authors: Min Li; Yuqing Zhang; Zijuan Liu; Uddalak Bharadwaj; Hao Wang; Xinwen Wang; Sheng Zhang; Juan P. Liuzzi; Shou-Mei Chang; Robert J. Cousins; William E. Fisher; F. Charles Brunic...; Craig D. Logsdon; Changyi Chen; Qizhi Yao
• Keywords: Pathogenesis; Tumor progression

Zinc is an essential trace element and catalytic/structural component used by many metalloenzymes transcription factors. Recent studies indicate a possible correlation of zinc levels with the cancer risk; however, exact role transporters in progression unknown. We have observed that transporter, ZIP4 (SLC39A4), was substantially overexpressed 16 17 (94%) clinical pancreatic adenocarcinoma specimens compared surrounding normal tissues, mRNA expression significantly higher human cells than ductal epithelium (HPDE) cells. This indicates aberrant up-regulation may contribute to pathogenesis progression. studied effects overexpression cell proliferation vitro vivo. found forced increased intracellular levels, 2-fold vitro, tumor volume 13-fold nude mice model s.c. xenograft control In orthotopic model, not only primary weight (7.2-fold), it also peritoneal dissemination ascites incidence. Moreover, content were tissues ZIP4. These data reveal important outcome contributing It suggest therapeutic strategy whereby targeted growth.