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Expression profiling of murine intestinal adenomas reveals early deregulation of multiple matrix metalloproteinase ( Mmp ) genes
Author(s) -
Martinez Cristina,
Bhattacharya Sumit,
Freeman Tom,
Churchman Michael,
Ilyas Mohammad
Publication year - 2005
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1755
Subject(s) - biology , matrilysin , matrix metalloproteinase , gene , gene expression , intestinal mucosa , gene expression profiling , intestinal epithelium , cancer research , epithelium , stroma , wnt signaling pathway , sulindac , pathology , genetics , immunology , medicine , immunohistochemistry , nonsteroidal , pharmacology
Initiation of intestinal tumours occurs as a consequence of aberrant Wnt signalling. This causes altered expression of a number of genes which provides the mechanistic basis of neoplastic change in normal epithelium. In order to identify these genes, expression profiles of normal intestinal mucosa and intestinal adenomas from multiple intestinal neoplasia (Min) mice were compared. A total of 116 genes were found to show significant changes in expression in adenomas compared with normal mucosa. Functional classification of these genes clearly identified the biological processes of cellular adhesion and matrix remodelling to be profoundly affected. Notably, three members of the matrix metalloproteinase ( Mmp ) gene family ( Mmp10, Mmp13 , and Mmp14 ) were consistently up‐regulated in tumour tissue. To extend these data, expression of 17 Mmp genes was defined using quantitative reverse transcriptase‐polymerase chain reaction (Q‐RT‐PCR). Several Mmp genes were profoundly up‐regulated and every tumour showed overexpression of at least four Mmp genes. These results underscore the probable importance of interactions between the intestinal epithelium and stroma in early tumour development. Furthermore, the inferred role of Mmps at the adenomatous stage of tumourigenesis suggests that this may represent the optimal therapeutic window for the use of Mmp antagonists as anti‐cancer agents. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.