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Science 17 February 1989:
Vol. 243. no. 4893, pp. 947 - 950
DOI: 10.1126/science.2465572
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Articles

Science, Vol 243, Issue 4893, 947-950
Copyright © 1989 by American Association for the Advancement of Science

articles

Antisense RNA-induced reduction in murine TIMP levels confers oncogenicity on Swiss 3T3 cells

R Khokha, P Waterhouse, S Yagel, PK Lala, CM Overall, G Norton, and DT Denhardt

Department of Biochemistry, University of Western Ontario, London, Canada.

Mouse 3T3 cell lines capable of constitutively synthesizing an RNA complementary to the messenger RNA encoding TIMP, tissue inhibitor of metalloproteinases, were constructed by transfection with appropriate plasmid constructs. Many of the lines were down-modulated for TIMP messenger RNA levels and secreted less TIMP into the culture medium. In comparison to noninvasive, nontumorigenic controls, these cells not only were invasive in a human amnion invasion assay, but also were tumorigenic and metastatic in athymic mice. These results indicate that TIMP suppresses oncogenicity, at least in immortal murine 3T3 cells.


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