期刊
MOLECULAR ONCOLOGY
卷 2, 期 3, 页码 233-240出版社
WILEY
DOI: 10.1016/j.molonc.2008.06.003
关键词
Colorectal cancer; TIMP-1; Gene expression profiling
类别
资金
- John and Birthe Meyer Foundation
- Raimond and Dagmar Ringgaard-Bohns Foundation
- The Danish Cancer Society
- The Danish Medical Research Counsel
- The Novo Nordisk Foundation
- The Beckett Foundation
- The Obel Family Foundation
- The Johannes Fog Foundation
- The Anders Kaaresens Foundation
- The IMK Foundation
- The Kathrine and Vigo Skovgaard Foundation
- A.P. Moller Foundation
The balance of activity between the endogenous enzyme inhibitors known as tissue inhibitors of metalloproteinases and their targets, the matrix metalloprotemases, in the extracellular matrix is thought to play an important role in tumour cell invasion. Supporting this notion, we have shown that colorectal cancer patients have increased plasma levels of the tissue inhibitor of metalloproteinases-1 (TIMP-1), and that high plasma TIMP-1 levels are associated with short colorectal cancer patient survival. However, although TIMP-1 has been extensively studied in cancer, very little is known about how it is regulated. To further elucidate potential mechanisms of regulation of this protein, we did a number of experiments to look at associations between the transcript profile of TIMP-1 with known matrix metalloproteinases (MMPs) as well as with expression profiles of other genes differentially regulated in human colorectal cancer (CRC) and the other TIMPs 2-4, which have also been associated with the progression of colorectal cancer. Genome-wide expression profiling of 172 CRC and normal mucosa samples was used to identify transcript changes for the genes under investigation. We found that TIMP-1 was up-regulated in CRC samples compared with normal tissue, while TIMP-2 was down-regulated. Eight MMPs were up-regulated in CRC compared with normal tissue. Correlating up-regulated genes with the TIMP-1 transcript, we identified 13 that were also up-regulated in cancerous tissue. Among these were genes associated with the synthesis of extracellullar matrix, genes involved in the TGF-beta signalling pathway, and genes that are likely transcribed by the tumour cells. These insights add to the complex picture emerging about the regulation of TIMPs in colorectal cancer. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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