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Increased expression of tissue inhibitor of metalloproteinases type 1 (TIMP‐1) in a more tumourigenic colon cancer cell line
Author(s) -
Hewitt Robert E.,
Brown Kevin E.,
Corcoran Marta,
StetlerStevenson William G.
Publication year - 2000
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 - 10.1002/1096-9896(2000)9999:9999<::aid-path777>3.0.co;2-e
Subject(s) - western blot , matrix metalloproteinase , colorectal cancer , cell culture , northern blot , biology , cancer research , gene expression , cancer , secretion , tissue inhibitor of metalloproteinase , messenger rna , gene , cell , suppressor , tumor suppressor gene , endocrinology , genetics , carcinogenesis
Genetic changes occurring in the late stages of colonic tumour progression have received much less attention than those occurring in the early stages. As described in the accompanying paper, SW480 and SW620 cell lines provide a useful model for studying the advanced stages of progression for colon cancer. Comparison of the two cell lines by differential display reveals that SW620 cells express lower levels of the CC3 tumour suppressor gene and also lower levels of the tissue inhibitor of metalloproteinases‐3 (TIMP‐3) gene. Northern blot analysis for TIMP‐3 confirms this finding and shows a similar difference in the expression of TIMP‐2, which seems logical since TIMPs inhibit enzymes that play a role in tumour invasion. For this reason, it was surprising to find that TIMP‐1 messenger RNA expression is markedly increased in SW620 cells. Consistent with this finding, western blot analysis shows a ten‐fold increase in TIMP‐1 protein secretion by SW620 cells. It is noteworthy that high TIMP‐1 expression is associated with poor prognosis in colorectal cancer. This association between TIMP‐1 expression and tumour progression may be related to additional growth factor‐like effects described for TIMP‐1 in some systems. Copyright © 2000 John Wiley & Sons, Ltd.