title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Medical Biochemistry and Genetics, University of Copenhagen, Blegdamsvej 3, Denmark. vogel@imbg.ku.dk
authors.forename: Lotte K
authors.initials: LK
authors.lastname: Vogel
authors.forename: Mona
authors.initials: M
authors.lastname: Saebø
authors.forename: Camilla F
authors.initials: CF
authors.lastname: Skjelbred
authors.forename: Kathrine
authors.initials: K
authors.lastname: Abell
authors.forename: Esben D K
authors.initials: ED
authors.lastname: Pedersen
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Elin H
authors.initials: EH
authors.lastname: Kure
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases / Q000032:analysis / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger; C109149:SPINT1 protein, human; D012697:Serine Endopeptidases; C485596:ST14 protein, human