In:
BMC Cancer, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2009-12)
Abstract:
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 . Methods 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. Results 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. Conclusion 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.
Type of Medium:
Online Resource
ISSN:
1471-2407
DOI:
10.1186/1471-2407-9-201
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2009
detail.hit.zdb_id:
2041352-X
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