This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Spence, S. L. Articles by Nissley, P. Search for Related Content PubMed PubMed Citation Articles by Spence, S. L. Articles by Nissley, P.

Transformation of Late Passage Insulin-Like Growth Factor-I Receptor Null Mouse Embryo Fibroblasts by SV40 T Antigen

Metabolism Branch, National Cancer Institute, NIH, Bethesda, Maryland

Requests for reprints: Peter Nissley, Metabolism Branch, National Cancer Institute, NIH, Building 10, Room 4N115, Bethesda, MD 20892. Phone: 301-530-3442; Fax: 301-496-9956; E-mail: spniss{at}mail.nih.gov.

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. (Cancer Res 2006; 66(8): 4233-9)