Antisense RNA--Induced Reduction in Murine TIMP Levels Confers Oncogenicity on Swiss 3T3 Cells

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 s...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1989-02, Vol.243 (4893), p.947-950
Main Authors: Khokha, Rama, Waterhouse, Paul, Yagel, Simcha, Lala, Peeyush K., Overall, Christopher M., Norton, Gill, Denhardt, David T.
Format: Article
Language:English
Subjects:
3T3 cells
Animals
Biochemistry
Biological and medical sciences
Cancer
Carcinogenesis
Cell Line
Cell lines
Cell regulation
Cell Transformation, Neoplastic
Cells, Cultured
Cellular control mechanisms
Enzyme Inhibitors - genetics
Enzyme Inhibitors - metabolism
Female
Fundamental and applied biological sciences. Psychology
Gene expression
Glycoproteins
House mouse
Messenger RNA
Metalloendopeptidases - antagonists & inhibitors
Mice
Mice as laboratory animals
Mice, Nude
Molecular and cellular biology
Molecular genetics
Neoplasm Metastasis
Pituitary Neoplasms - genetics
Pituitary Neoplasms - pathology
Plasmids
RNA
RNA - genetics
RNA, Antisense
RNA, Messenger - antagonists & inhibitors
RNA, Messenger - genetics
Swiss 3T3 cells
Tissue Inhibitor of Metalloproteinases
Transfection
Tumor cell line
Tumors
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Description
Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.2465572