The androgen-regulated Calcium-Activated Nucleotidase 1 (CANT1) is commonly overexpressed in prostate cancer and is tumor-biologically relevant in vitro.

Abstract

Previously, we identified the calcium-activated nucleotidase 1 (CANT1) transcript as up-regulated in prostate cancer. Now, we studied CANT1 protein expression in a large cohort of nearly 1000 prostatic tissue samples including normal tissue, prostatic intraepithelial neoplasia (PIN), primary carcinomas, metastases, and castrate-resistant carcinomas, and further investigated its functional relevance. CANT1 displayed predominantly a Golgi-type immunoreactivity with additional and variable cytoplasmic staining. In comparison to normal tissues, the staining intensity was significantly increased in PIN lesions and cancer. In cancer, high CANT1 levels were associated with a better prognosis, and castrate-resistant carcinomas commonly showed lower CANT1 levels than primary carcinomas. The functional role of CANT1 was investigated using RNA interference in two prostate cancer cell lines with abundant endogenous CANT1 protein. On CANT1 knockdown, a significantly diminished cell number and DNA synthesis rate, a cell cycle arrest in G(1) phase, and a strong decrease of cell transmigration rate and wound healing capacity of CANT1 knockdown cells was found. However, on forced CANT1 overexpression, cell proliferation and migration remained unchanged. In summary, CANT1 is commonly overexpressed in the vast majority of primary prostate carcinomas and in the precursor lesion PIN and may represent a novel prognostic biomarker. Moreover, this is the first study to demonstrate a functional involvement of CANT1 in tumor biology.

• Authors: Josefine Gerhardt, Corinna Steinbrech, Oralea Büchi, Silvia Behnke, Annette Bohnert, Florian Fritzsche, Heike Liewen, Frank Stenner, Peter Wild, Thomas Hermanns, Michael Müntener, Manfred Dietel, Klaus Jung, Carsten Stephan, Glen Kristiansen
• Journal: The American journal of pathology (Am J Pathol) Vol. 178 Issue 4 Pg. 1847-60 (Apr 2011) ISSN: 1525-2191 [Electronic] United States
• PMID: 21435463 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Androgens
• Biomarkers, Tumor
• CANT1 protein, human
• Nucleotidases

Topics

• Aged
• Androgens (metabolism)
• Biomarkers, Tumor
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• G1 Phase
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• In Vitro Techniques
• Male
• Middle Aged
• Nucleotidases (biosynthesis)
• Prognosis
• Prostatic Intraepithelial Neoplasia (metabolism)
• Prostatic Neoplasms (metabolism)
• RNA Interference