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Open Access Research article

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

Lotte K Vogel1*, Mona Sæbø2, Camilla F Skjelbred23, Kathrine Abell1, Esben DK Pedersen1, Ulla Vogel4 and Elin H Kure25

Author Affiliations

1 Department of Medical Biochemistry and Genetics, University of Copenhagen, Blegdamsvej 3, Denmark

2 Telemark University College, Faculty of Arts and Sciences, Bø i Telemark, Norway

3 Department of Laboratory Medicine, Section of Medical Genetics, Telemark Hospital, Skien, Norway

4 National Institute of Occupational Health, Copenhagen, Denmark

5 Department of Pathology, Ullevaal University Hospital, Oslo, Norway

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BMC Cancer 2006, 6:176  doi:10.1186/1471-2407-6-176

Published: 4 July 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.