Embryology Research Today is a free monthly online journal that collates and summarizes the latest research about Embryology, including details on stem cells, reproduction, transplants, cloning.

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

Spence SL, Shaffer AL, Staudt LM, Amde S, Manney S, Terry C, Weisz K, Nissley P

Metabolism Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.

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.

Published 18 April 2006 in Cancer Res, 66(8): 4233-9.
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