Holzer Alison K, Varki Nissi M, Le Quynh T, Gibson Michael A, Naredi Peter, Howell Stephen B
Department of Medicine and Pathology and the Rebecca and John Moores Cancer Center, University of California, San Diego, 3855 Health Sciences Drive, La Jolla, CA 92093-0819, USA, and Department of Surgery, Umea University Hospital, Sweden.
J Histochem Cytochem. 2006 Sep;54(9):1041-9. doi: 10.1369/jhc.6A6970.2006. Epub 2006 May 18.
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 alpha 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.
主要的铜流入转运体——铜转运蛋白1（hCTR1），控制着顺铂在哺乳动物细胞中的细胞内蓄积。本研究的目的是确定hCTR1在正常和恶性人类组织中的表达模式。使用标准免疫组织化学技术，用针对hCTR1的特异性抗体对组织芯片进行染色。在胰岛的α细胞、胃黏膜和细支气管的肠内分泌细胞、甲状腺的C细胞以及垂体前叶的一部分细胞中观察到特别强烈的染色。恶性组织中hCTR1染色的频率和强度反映了其正常组织对应物中的水平。例如，正常前列腺组织和前列腺癌均不表达hCTR1，而其在正常结肠上皮和结肠癌中均普遍表达。在少数类癌、尤因肉瘤和未分化癌病例中观察到强染色。尽管所有组织都需要铜，但hCTR1的表达在正常组织和主要人类恶性肿瘤中高度可变，在肠内分泌细胞中发现的水平最高。在几种常见类型的癌症中未发现hCTR1表达，这表明hCTR1表达通常不会因转化而增强。
