Claudin-16 reduces the aggressive behavior of human breast cancer cells.

Abstract

Claudin-16 (Paracellin-1) is a transmembrane tight junction (TJ) protein originally described as having a critical role in the re-absorption of magnesium and calcium in the kidney. This study examined expression of Claudin-16 in human breast cells and tissues to identify a possible link between expression and aggressiveness in cells and between Claudin-16 levels and patient prognosis. Insertion of the Claudin-16 gene into MDA-MB-231 human breast cancer cells resulted in cells that were significantly less motile and invasive in behavior, with increased adhesion to matrix. These cells also exhibited significantly increased TJ functionality and "tighter" colony morphology. Moreover, growth rates were reduced in both in vitro and in vivo assays (P < 0.002). Frozen sections from breast cancer primary tumors (matched tumor 124 and background 33) were immuno-stained. RNA was reverse transcribed and analyzed by Q-PCR (standardized using beta-actin, normalized with cytokeratin-19 levels). Levels of expression of Claudin-16 were significantly decreased in node positive tumors compared to negative (P = 0.016). Expression was significantly lower in patients with node positive tumors (P = 0.016) and in those who had died from breast cancer or had general poor prognosis (P < 0.015). Immunohistochemical staining showed decreased expression of Claudin-16 in tumor sections (P < 0.00001). In conclusion, forced expression of Claudin-16 in breast cancer cells resulted in a less aggressive phenotype and reduced in vivo tumor volume. Claudin-16 expression was reduced in human breast cancer, particularly in patients with aggressive tumors and high mortality. This suggests that Claudin-16 plays a role beyond that of an initial metastasis repressor in this cancer type.

• Authors: Tracey A Martin, Gregory M Harrison, Gareth Watkins, Wen G Jiang
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 105 Issue 1 Pg. 41-52 (Sep 01 2008) ISSN: 1097-4644 [Electronic] United States
• PMID: 18442037 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2008 Wiley-Liss, Inc.

Chemical References

• Claudins
• Membrane Proteins
• RNA, Messenger
• claudin 16

Topics

• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Claudins
• Disease Progression
• Epithelial Cells (metabolism)
• Follow-Up Studies
• Gene Expression Regulation, Neoplastic
• Humans
• Membrane Proteins (genetics, metabolism)
• Neoplasm Invasiveness (genetics, pathology)
• Neoplasm Staging
• Phenotype
• RNA, Messenger (genetics)
• Time Factors
• Treatment Outcome