Open Access Research article

Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis

Joanna Selzer-Plon1, Jette Bornholdt1, Stine Friis1, Hanne C Bisgaard1, Inger MB Lothe2, Kjell M Tveit3, Elin H Kure234, Ulla Vogel5 and Lotte K Vogel1*

Author Affiliations

1 Department of Cellular and Molecular Medicine, Faculty of Health Science, University of Copenhagen, Denmark

2 Department of Pathology, Ulleval University Hospital, Oslo, Norway

3 The Cancer Centre, Ulleval University Hospital, 0407 Oslo, Norway

4 Department of Environmental and Health Studies, Telemark University College, Bø, Norway

5 National Food Institute, Technical University of Denmark, Soborg, Denmark and the National Research Centre for the Working Environment, Copenhagen, Denmark

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BMC Cancer 2009, 9:201  doi:10.1186/1471-2407-9-201

Published: 25 June 2009



Clinical trials where cancer patients were treated with protease inhibitors have suggested that the serine protease, prostasin, may act as a tumour suppressor. Prostasin is proteolytically activated by the serine protease, matriptase, which has a very high oncogenic potential. Prostasin is inhibited by protease nexin-1 (PN-1) and the two isoforms encoded by the mRNA splice variants of hepatocyte growth factor activator inhibitor-1 (HAI-1), HAI-1A, and HAI-1B.


Using quantitative RT-PCR, we have determined the mRNA levels for prostasin and PN-1 in colorectal cancer tissue (n = 116), severe dysplasia (n = 13), mild/moderate dysplasia (n = 93), and in normal tissue from the same individuals. In addition, corresponding tissues were examined from healthy volunteers (n = 23). A part of the cohort was further analysed for the mRNA levels of the two variants of HAI-1, here denoted HAI-1A and HAI-1B. mRNA levels were normalised to β-actin. Immunohistochemical analysis of prostasin and HAI-1 was performed on normal and cancer tissue.


The mRNA level of prostasin was slightly but significantly decreased in both mild/moderate dysplasia (p < 0.001) and severe dysplasia (p < 0.01) and in carcinomas (p < 0.05) compared to normal tissue from the same individual. The mRNA level of PN-1 was more that two-fold elevated in colorectal cancer tissue as compared to healthy individuals (p < 0.001) and elevated in both mild/moderate dysplasia (p < 0.01), severe dysplasia (p < 0.05) and in colorectal cancer tissue (p < 0.001) as compared to normal tissue from the same individual. The mRNA levels of HAI-1A and HAI-1B mRNAs showed the same patterns of expression. Immunohistochemistry showed that prostasin is located mainly on the apical plasma membrane in normal colorectal tissue. A large variation was found in the degree of polarization of prostasin in colorectal cancer tissue.


These results show that the mRNA level of PN-1 is significantly elevated in colorectal cancer tissue. Future studies are required to clarify whether down-regulation of prostasin activity via up regulation of PN-1 is causing the malignant progression or if it is a consequence of it.