Transformation of late passage insulin-like growth factor-I receptor null mouse embryo fibroblasts by SV40 T antigen

• Published in: Cancer research (Chicago, Ill.) Vol. 66; no. 8; pp. 4233 - 4239
• Main Authors: SPENCE, Susan L, SHAFFER, Arthur L, STAUDT, Louis M, AMDE, Sewit, MANNEY, Sutana, TERRY, Cheryl, WEISZ, Keith, NISSLEY, Peter
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-04-2006
• Subjects: Animals; Antigens, Polyomavirus Transforming - genetics; Antigens, Polyomavirus Transforming - physiology; Antineoplastic agents; Biological and medical sciences; Cell Growth Processes - physiology; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; DNA - biosynthesis; Embryo, Mammalian; Fibroblasts - metabolism; Fibroblasts - pathology; Fibroblasts - physiology; Focal Adhesion Kinase 1 - metabolism; Genotype; GRB2 Adaptor Protein - biosynthesis; GRB2 Adaptor Protein - genetics; Insulin Receptor Substrate Proteins; Ligands; Medical sciences; Mice; Mice, Knockout; Pharmacology. Drug treatments; Phosphoproteins - biosynthesis; Phosphoproteins - genetics; Phosphorylation; Receptor, ErbB-3 - biosynthesis; Receptor, ErbB-3 - genetics; Receptor, IGF Type 1 - deficiency; Receptor, IGF Type 1 - genetics; Receptor, IGF Type 1 - metabolism; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Simian virus 40; Transfection; Tumors; Embryo; Late; Polyomavirus; Rodentia; Papovaviridae; Insulin like growth factor 1; Passage; Simian virus 40; Virus; Antigen; Vertebrata; Mammalia; Mouse; Animal; Fibroblast; Biological receptor
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-05-2257

There is evidence that the insulin-like growth factor-I (IGF-I) receptor is required for transformation by a variety of viral and cellular oncogenes in a mouse embryo fibroblast model. To further investigate the IGF-I receptor signaling pathways that are required for the permissive effect of the receptor on transformation by SV40 T antigen, we established three independent fibroblast cell lines each from wild-type and IGF-I receptor null embryos (R-). We transfected the wild-type and R- cell lines with an SV40 T antigen plasmid and selected three clones from each cell line that expressed T antigen. As in previous reports, none of the cloned R- cell lines expressing T antigen were transformed as measured by the ability to form large colonies in soft agar. However, with further passage, all three T antigen-expressing clones from one of the R- cell lines (R(-)3) formed large colonies in soft agar and the transformation of these T antigen-expressing clones was confirmed by tumorigenesis experiments in immunodeficient mice. DNA microarray analysis comparing gene expression between early passage and late passage R(-)3/T antigen clones showed, among other changes, an increase in the expression of ErbB-3 mRNA in the late passage clones. Also, the expression of ErbB-3 protein was dramatically increased in the late passage R(-)3/T antigen clones. We conclude that late passage IGF-I receptor null mouse embryo fibroblasts can be transformed by SV40 T antigen, and that ErbB-3 may play a role in permitting transformation by T antigen.