Transformation of late passage insulin-like growth factor-I receptor null mouse embryo fibroblasts by SV40 T antigen.
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.
Spence
Susan L
SL
Metabolism Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Shaffer
Arthur L
AL
Staudt
Louis M
LM
Amde
Sewit
S
Manney
Sutana
S
Terry
Cheryl
C
Weisz
Keith
K
Nissley
Peter
P
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000502:physiology*; D048708:Cell Growth Processes / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004247:DNA / Q000096:biosynthesis; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D051380:GRB2 Adaptor Protein / Q000096:biosynthesis / Q000235:genetics; D005838:Genotype; D055504:Insulin Receptor Substrate Proteins; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020893:Receptor, ErbB-3 / Q000096:biosynthesis / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D008024:Ligands; D010750:Phosphoproteins; D012333:RNA, Messenger; D004247:DNA; D020893:Receptor, ErbB-3; D017526:Receptor, IGF Type 1; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse