Simultaneous determination of matrix metalloproteinase (MMP)-7, MMP-1, -3, and -13 gene expression by multiplex PCR in colorectal carcinomas

Int J Colorectal Dis. 2004 Nov;19(6):518-24. doi: 10.1007/s00384-004-0592-6. Epub 2004 Apr 22.

Abstract

Background and aims: 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).

Materials and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Cell Proliferation
  • Collagenases / biosynthesis*
  • Collagenases / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • DNA, Neoplasm / analysis
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Matrix Metalloproteinase 1 / biosynthesis*
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 3 / biosynthesis*
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinase 7 / biosynthesis*
  • Matrix Metalloproteinase 7 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods

Substances

  • DNA, Neoplasm
  • Collagenases
  • MMP13 protein, human
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 7
  • Matrix Metalloproteinase 1