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Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis

BACKGROUND: 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...

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Autores principales: Selzer-Plon, Joanna, Bornholdt, Jette, Friis, Stine, Bisgaard, Hanne C, Lothe, Inger MB, Tveit, Kjell M, Kure, Elin H, Vogel, Ulla, Vogel, Lotte K
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717118/
https://www.ncbi.nlm.nih.gov/pubmed/19555470
http://dx.doi.org/10.1186/1471-2407-9-201
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author Selzer-Plon, Joanna
Bornholdt, Jette
Friis, Stine
Bisgaard, Hanne C
Lothe, Inger MB
Tveit, Kjell M
Kure, Elin H
Vogel, Ulla
Vogel, Lotte K
author_facet Selzer-Plon, Joanna
Bornholdt, Jette
Friis, Stine
Bisgaard, Hanne C
Lothe, Inger MB
Tveit, Kjell M
Kure, Elin H
Vogel, Ulla
Vogel, Lotte K
author_sort Selzer-Plon, Joanna
collection PubMed
description BACKGROUND: 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.
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spelling pubmed-27171182009-07-29 Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis Selzer-Plon, Joanna Bornholdt, Jette Friis, Stine Bisgaard, Hanne C Lothe, Inger MB Tveit, Kjell M Kure, Elin H Vogel, Ulla Vogel, Lotte K BMC Cancer Research Article BACKGROUND: 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. BioMed Central 2009-06-25 /pmc/articles/PMC2717118/ /pubmed/19555470 http://dx.doi.org/10.1186/1471-2407-9-201 Text en Copyright ©2009 Selzer-Plon et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Selzer-Plon, Joanna
Bornholdt, Jette
Friis, Stine
Bisgaard, Hanne C
Lothe, Inger MB
Tveit, Kjell M
Kure, Elin H
Vogel, Ulla
Vogel, Lotte K
Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis
title Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis
title_full Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis
title_fullStr Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis
title_full_unstemmed Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis
title_short Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis
title_sort expression of prostasin and its inhibitors during colorectal cancer carcinogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717118/
https://www.ncbi.nlm.nih.gov/pubmed/19555470
http://dx.doi.org/10.1186/1471-2407-9-201
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