title: hZIP1 zinc transporter down-regulation in prostate cancer involves the overexpression of ras responsive element binding protein-1 (RREB-1).
abstract: BACKGROUND
  A marked decrease in the level of zinc is a consistent characteristic of prostate cancer; which results from down-regulation of ZIP1 zinc transporter. The aim of this study was to determine if RREB-1 transcription is involved in the down-regulation of ZIP1 gene expression; and to determine the expression of RREB-1 in benign and cancerous prostate in situ.
  
  
  METHODS
  Overexpression and siRNA knock down of RREB-1 were used to determine the effect of RREB-1 on hZIP1 abundance in PC-3 cells. Immunohistochemistry with tissue microarrays (TMAs) and tissue sections was used to determine the levels of RREB-1 expression in prostate in situ.
  
  
  RESULTS
  Overexpression of RREB-1 resulted in a decrease in the abundance of hZIP1 in the plasma membrane of PC-3 cells; whereas siRNA knock down significantly increased hZIP1 expression. Prostate TMAs and tissue sections showed an inverse relationship between RREB-1 and hZIP1 staining.
  
  
  CONCLUSIONS
  RREB-1 overexpression results in down-regulation of hZIP1 and contributes to the loss of hZIP1 expression and zinc in prostate cancer. This is an early event in prostate carcinogenesis.
authors.affiliation: Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland Baltimore, Baltimore, Maryland.
authors.forename: Jing
authors.initials: J
authors.lastname: Zou
authors.forename: Beatrice C
authors.initials: BC
authors.lastname: Milon
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Desouki
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Costello
authors.forename: Renty B
authors.initials: RB
authors.lastname: Franklin
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D001706:Biopsy; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D044127:Epigenesis, Genetic / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; C101743:RREB1 protein, human; C403517:SLC39A1 protein, human; D014157:Transcription Factors; D015032:Zinc