Article
Lab Invest 2002, 82:1755–1764
Calcium-Selective Ion Channel, CaT1, Is Apically Localized in Gastrointestinal Tract Epithelia and Is Aberrantly Expressed in Human Malignancies
The first two authors contributed equally.
Liyan Zhuang1, Ji-Bin Peng2,3, Liqiang Tou4, Hitomi Takanaga2,3, Rosalyn M Adam1, Matthias A Hediger2,3 and Michael R Freeman1
- 1The Urologic Laboratory, Department of Urology, Children's Hospital Boston, Boston, Massachusetts
- 2Department of Surgery, Harvard Medical School, Membrane Biology Program, Boston, Massachusetts
- 3Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
- 4Harvard-Thorndike and Charles A. Dana Research Laboratories, Division of Bone and Mineral Metabolism, Department of Medicine, Beth Israel Medical Center, Harvard Medical School, Boston, Massachusetts
Correspondence: Dr. Michael R. Freeman, Enders Research Laboratories, Room 1161, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115. E-mail: Michael.Freeman@tch.harvard.edu
Received 26 September 2002.
Abstract
CaT1 is a highly selective calcium entry channel that has been proposed to be responsible for apical calcium entry in the vitamin D-regulated transcellular pathway of Ca2+ absorption; however, the lack of a CaT1 antibody suitable for immunohistochemistry has prevented the direct testing of this hypothesis by the localization of CaT1 protein in the gastrointestinal tract and other tissues. In this study, we developed two CaT1 antibodies and have used them to establish for the first time that CaT1 localizes to the apical membrane of intestinal absorptive cells, thereby providing the first direct evidence that this protein is in fact an apical entry channel in the gastrointestinal tract. In addition, we found that CaT1 protein is highly expressed in a number of exocrine organs including pancreas, prostate, and mammary gland, suggesting an, as yet, unrecognized role in secretory epithelia. Finally, we found CaT1 protein to be present at elevated levels in comparison with normal tissues in a series of prostate, breast, thyroid, colon, and ovarian carcinomas, consistent with previous reports of up-regulation of CaT1 mRNA in prostate cancer tissues. Our findings indicate that CaT1 is likely to serve as a component of transcellular calcium transport mechanisms in many tissues and epithelial cancers.
