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




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BMC Cancer

, 6:176

First Online: 04 July 2006Received: 30 March 2006Accepted: 04 July 2006DOI: 10.1186-1471-2407-6-176

Cite this article as: Vogel, L.K., Sæbø, M., Skjelbred, C.F. et al. BMC Cancer 2006 6: 176. doi:10.1186-1471-2407-6-176

Abstract

BackgroundIt 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.

MethodsUsing 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.

ResultsMatriptase 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.

ConclusionOur 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.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-6-176 contains supplementary material, which is available to authorized users.

Mona Sæbø, Camilla F Skjelbred contributed equally to this work.

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

Fuente: https://link.springer.com/







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