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Journal article
Simian Virus 40 Large Tumor Antigen is Unable to Transform Mouse Embryonic Fibroblasts Lacking Type 1 Insulin-Like Growth Factor Receptor
Proceedings of the National Academy of Sciences - PNAS, v 90(23), pp 11217-11221
01 Dec 1993
PMID: 8248231
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Abstract
Fibroblast cell lines were established from mouse embryos homozygous for a targeted disruption of the Igf1r gene, encoding the type 1 receptor for insulin-like growth factor I (IGF-I) and from their wild-type littermates. The cells from the wild-type embryos (W cells) grow in serum-free medium supplemented with platelet-derived growth factor, epidermal growth factor, and IGF-I, whereas the cells from Igf1r(-/-) embryos (R-cells) do not, although they grow at a reduced rate in 10% fetal calf serum. The simian virus 40 (SV40) large T antigen, expressed from a transfected plasmid, can transform W cells, which form foci in monolayer cultures and colonies in soft agar (anchorage-independent growth). In contrast, the SV40 large tumor antigen, although normally expressed from the transfected template, is unable to transform R-cells, which remain contact-inhibited and fail to grow in soft agar. The transformed phenotype is restored if the R-cells carrying the SV40 large tumor antigen are stably transfected with a plasmid expressing the human IGF-I receptor. These results demonstrate that signaling via the IGF-I receptor is an indispensable component of the SV40 transformation pathway. This conclusion is further supported from the results of antisense RNA experiments with tumor cell lines showing that interference with the function of the IGF-I receptor has a profound effect on anchorage-independent growth, even under conditions that only modestly affect growth in monolayers.
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Details
- Title
- Simian Virus 40 Large Tumor Antigen is Unable to Transform Mouse Embryonic Fibroblasts Lacking Type 1 Insulin-Like Growth Factor Receptor
- Creators
- Christian Sell - Thomas Jefferson UniversityMichele RubiniRaphael RubinJeh-Ping LiuArgiris EfstratiadisRenato Baserga
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 90(23), pp 11217-11221
- Publisher
- National Academy of Sciences of the United States of America
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:A1993MK09400069
- Scopus ID
- 2-s2.0-0027366338
- Other Identifier
- 991020111326004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology