Primary research

Epithelial Na, K-ATPase expression is down-regulated in canine prostate cancer; a possible consequence of metabolic transformation in the process of prostate malignancy

Ali Mobasheri¹ , Richard Fox² , Iain Evans¹ , Fay Cullingham¹ , Pablo Martín-Vasallo³ and Christopher S Foster⁴

¹  Molecular Pathogenesis Research Group, Department of Veterinary Preclinical Sciences, Faculty of Veterinary Science, University of Liverpool, Liverpool L69 7ZJ, United Kingdom

²  Department of Veterinary Pathology, Faculty of Veterinary Science, University of Liverpool, Liverpool L69 7ZJ, United Kingdom

³  Labratorio de Biología del Desarollo, Departamento de Bioquímica y Biología Molecular, Universidad de La Laguna, 38201 La Laguna, Tenerife, Spain

⁴  Department of Cellular and Molecular Pathology, Faculty of Medicine, University of Liverpool, Liverpool L69 3GA, United Kingdom

author email corresponding author email

Cancer Cell International 2003, 3:8doi:10.1186/1475-2867-3-8

Published:	13 June 2003

Abstract

Background

An important physiological function of the normal prostate gland is the synthesis and secretion of a citrate rich prostatic fluid. In prostate cancer, citrate production levels are reduced as a result of altered cellular metabolism and bioenergetics. Na, K-ATPase is essential for citrate production since the inward Na⁺ gradients it generates are utilized for the Na⁺ dependent uptake of aspartate, a major substrate for citrate synthesis. The objective of this study was to compare the expression of previously identified Na, K-ATPase isoforms in normal canine prostate, benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma (PCa) using immunohistochemistry in order to determine whether reduced citrate levels in PCa are also accompanied by changes in Na, K-ATPase expression.

Results

Expression of Na, K-ATPase α1 and β1 isoforms was observed in the lateral and basolateral plasma membrane domains of prostatic epithelial cells in normal and BPH prostates. Canine kidney was used as positive control for expression of Na, K-ATPase α1 and γ isoforms. The α1 isoform was detected in abundance in prostatic epithelial cells but there was no evidence of α2, α3 or γ subunit expression. In advanced PCa, Na, K-ATPase α1 isoform expression was significantly lower compared to normal and BPH glands. The abundant basolateral immunostaining observed in normal and BPH tissue was significantly attenuated in PCa.

Conclusion

The loss of epithelial structure and function and the transformation of normal epithelial cells to malignant cells in the canine prostate have important implications for cellular metabolism and are accompanied by a down regulation of Na, K-ATPase.