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

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 beta-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.

• Authors: Lotte K Vogel, Mona Saebø, Camilla F Skjelbred, Kathrine Abell, Esben D K Pedersen, Ulla Vogel, Elin H Kure
• Journal: BMC cancer (BMC Cancer) Vol. 6 Pg. 176 (Jul 04 2006) ISSN: 1471-2407 [Electronic] England
• PMID: 16820046 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Glycoproteins
• Proteinase Inhibitory Proteins, Secretory
• RNA, Messenger
• SPINT1 protein, human
• Serine Endopeptidases
• ST14 protein, human

Topics

• Adenoma (metabolism, pathology)
• Carcinoma (metabolism, pathology)
• Case-Control Studies
• Cell Transformation, Neoplastic
• Colorectal Neoplasms (metabolism, pathology)
• Female
• Gene Expression Profiling
• Humans
• Male
• Membrane Glycoproteins (analysis, metabolism)
• Middle Aged
• Proteinase Inhibitory Proteins, Secretory
• RNA, Messenger (analysis)
• Serine Endopeptidases (analysis, metabolism)