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BMC Cancer

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Open Access 01-12-2006 | Research article

The ratio of Matriptase/HAI-1mRNA is higher in colorectal cancer adenomas and carcinomas than corresponding tissue from control individuals

Authors: Lotte K Vogel, Mona Sæbø, Camilla F Skjelbred, Kathrine Abell, Esben DK Pedersen, Ulla Vogel, Elin H Kure

Published in: BMC Cancer | Issue 1/2006

Abstract

Background

It has recently been shown that overexpression of the serine protease, matriptase, in transgenic mice causes a dramatically increased frequency of carcinoma formation. Overexpression of HAI-1 and matriptase together changed the frequency of carcinoma formation to normal. This suggests that the ratio of matriptase to HAI-1 influences the malignant progression. The aim of this study has been to determine the ratio of matriptase to HAI-1 mRNA expression in affected and normal tissue from individuals with colorectal cancer adenomas and carcinomas as well as in healthy individuals, in order to determine at which stages a dysregulated ratio of matriptase/HAI-1 mRNA is present during carcinogenesis.

Methods

Using quantitative RT-PCR, we have determined the mRNA levels for matriptase and HAI-1 in colorectal cancer tissue (n = 9), severe dysplasia (n = 15), mild/moderate dysplasia (n = 21) and in normal tissue from the same individuals. In addition, corresponding tissue was examined from healthy volunteers (n = 10). Matriptase and HAI-1 mRNA levels were normalized to β-actin.

Results

Matriptase mRNA level was lower in carcinomas compared to normal tissue from healthy individuals (p < 0.01). In accordance with this, the matriptase mRNA level was also lower in adenomas/carcinomas combined as compared to their adjacent normal tissue (p < 0.01). HAI-1 mRNA levels in both normal and affected tissue from individuals with severe dysplasia or carcinomas and in affected tissue with mild/moderate dysplasia were all significantly lower than mRNA levels observed in corresponding tissue from healthy control individuals. HAI-1 mRNA was lower in carcinomas as compared to normal tissue from healthy individuals (p < 0.001). HAI-1 mRNA levels were significantly lower in tissue displaying mild/moderate (p < 0.001) and severe (p < 0.01) dysplasia compared to normal tissue from the same patients. Both adenomas and carcinomas displayed a significantly different matriptase/HAI-1 mRNA ratio than corresponding normal tissue from healthy control individuals (p < 0.05). In addition statistically significant difference (p < 0.001) could be observed between mild/moderate and severe adenomas and their adjacent normal tissue.

Conclusion

Our results show that dysregulation of the matriptase/HAI-1 mRNA ratio occurs early during carcinogenesis. Future studies are required to clarify whether the dysregulated matriptase/HAI-1 ratio was causing the malignant progression or is a consequence of the same.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/6/176/prepub

Title: The ratio of Matriptase/HAI-1mRNA is higher in colorectal cancer adenomas and carcinomas than corresponding tissue from control individuals
Authors: Lotte K Vogel
Mona Sæbø
Camilla F Skjelbred
Kathrine Abell
Esben DK Pedersen
Ulla Vogel
Elin H Kure
Publication date: 01-12-2006
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2006
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-6-176

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