Simultaneous determination of matrix metalloproteinase (MMP)-7, MMP-1, -3, and -13 gene expression by multiplex PCR in colorectal carcinomas.
OBJECTIVE
MMP-7, a member of the matrix metalloproteinase family, is believed to play a significant role in the growth and proliferation of colon cancer cells. The aim of this study was to evaluate MMP-7 gene expression in comparison with MMP-1, MMP-3, and MMP-13 in patients with resectable rectal and colon cancer by a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).


METHODS
Biopsy samples of tumor ( n=30) and distant normal mucosa ( n=30) from 30 patients were obtained intraoperation. Messenger (m)RNA was extracted from all of the tissue samples and reverse transcribed to double-stranded cDNA. Semi-quantitative RT-PCR was performed to study the MMP gene expression in both the tumor and normal mucosal specimens. MMP mRNA values were expressed relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for each sample.


RESULTS
In all 30 cases an increase in MMP-7 mRNA expression was detected in the cancerous tissue ( p=0.00004). In 21 out of 30 cases an increase in MMP-13 mRNA ( p=0.023) and in 22 out of 30 cases an increase in MMP-3 mRNA ( p=0.075) was detected in the cancerous tissue. In contrast, there was no significant change in the MMP-1 expression of normal and cancerous mucosal specimens in either colon or rectal carcinomas. There were no significant differences between rectum and colon carcinomas.


CONCLUSIONS
Taking into account our earlier studies, we conclude that most cases of colorectal carcinogenesis are characterized by enhanced expression of MMP-7, -13, -3 and the gelatinases, whereas MMP-1-expression is very inconsistent and not overexpressed in many cases. MMP-7 inhibition as well as inhibition of MMP-13 and MMP-3 may be a useful preventive or therapeutic adjunct in colorectal cancer.
Roeb
Elke
E
Medical Clinic III, Rheinisch-Westfälische Technische Hochschule Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany. eroeb@ukaachen.de.
Arndt
Marlies
M
Jansen
Bettina
B
Schumpelick
Volker
V
Matern
Siegfried
S
D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D017364:Collagenases / Q000096:biosynthesis* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000235:genetics; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D004273:DNA, Neoplasm; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7; D020781:Matrix Metalloproteinase 1