Characterization of the hZip1 promoter in prostate cancer cells

• Published in: The FASEB journal 2007-04, Vol.21 (5), p.A285-A286
• Main Authors: Milon, Beatrice C, Agyapong, Anthony A, Bautista, Roderick, Costello, Leslie C, Franklin, Renty B
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.21.5.A285

Normal prostate accumulates high levels of zinc compared to other soft tissues. On the other hand, the level of zinc in the prostate decreases significantly in prostate cancer. We have shown that the zinc importer, hZip1, is down regulated in adenocarcinomatous glands compared to normal prostate. These data lead us to suggest that down regulation of hZip1 is one of the events responsible for the decrease of zinc levels in prostate cancer. To investigate the mechanisms of hZip1 down‐regulation, we identified its promoter region. 5′RACE using RNA from PC‐3 cells revealed two distinct transcription start sites corresponding to a transcript with four exons and another with only three exons. Reporter gene assays allowed us to locate the minimal promoter and a downstream region that inhibits completely the expression of the reporter gene. hZip1 down‐regulation is likely due to a reversible mechanism because its expression is restored in prostate cell lines derived from metastasis. Epigenetic modifications such as promoter methylation play an important role in cancer development. Therefore we decided to investigate the methylation status of the hZip1 promoter in prostate samples. Preliminary data suggest the presence of hypermethylation of the promoter in prostate cancer tissues. NIH/NCI RO1 CA79903