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Expression of the Human Copper Influx Transporter 1 in Normal and Malignant Human Tissues

Alison K. Holzer, Nissi M. Varki, Quynh T. Le, Michael A. Gibson, Peter Naredi and Stephen B. Howell

Department of Medicine and Pathology and the Rebecca and John Moores Cancer Center, University of California, San Diego, La Jolla, California (AKH,NMV,QTL,MAG,SBH), and Department of Surgery, Umea University Hospital, Umea, Sweden (PN)

Correspondence to: Stephen B. Howell, MD, Department of Medicine 0819, University of California, San Diego, 3855 Health Sciences Drive, La Jolla, CA 92093-0819. E-mail: showell{at}ucsd.edu

The major copper influx transporter, copper transporter 1 (hCTR1), controls the cellular accumulation of cisplatin in mammalian cells. The goal of this study was to determine the pattern of hCTR1 expression in normal and malignant human tissues. Tissue arrays were stained with an antibody specific for hCTR1 using standard immunohistochemical techniques. Particularly strong staining was noted in the cells of the pancreatic islets, enteroendocrine cells of the gastric mucosa and bronchioles, C cells of the thyroid, and a subset of cells in the anterior pituitary. Frequency and intensity of hCTR1 staining in malignant tissues reflected the levels found in their normal tissue counterparts. For example, neither normal prostate nor prostate cancers expressed hCTR1, whereas it was commonly expressed in both normal colonic epithelium and in colon carcinomas. Strong staining was observed in a limited number of cases of carcinoid tumors, Ewing's sarcoma, and undifferentiated carcinomas. Although all tissues require copper, expression of hCTR1 was highly variable among normal tissues and among the major human malignancies, with the highest levels found in enteroendocrine cells. No hCTR1 expression was found in several common types of cancer, suggesting that hCTR1 expression is not commonly enhanced by transformation. (J Histochem Cytochem 54:1041–1049, 2006)

Key Words: copper • cisplatin • tumor expression • transporter

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