For example, the amino-terminal region of T antigen (Fig. Transformation induced by T antigen is accomplished by targeting cellular components. Expression of this viral protein is sufficient to transform multiple primary cell types (reviewed in references 19 and 47), and when expressed ectopically in transgenic mice, it causes neoplasia in numerous tissues (reviewed in reference 47). Large T antigen (TAg), an oncogene encoded by the small DNA tumor virus simian virus 40 (SV40), is a powerful tool for elucidating the mechanisms of growth regulation and control of cell proliferation. Rather, some unknown function of T antigen is essential for progression beyond hyperplasia. These data indicate that loss of p53 function does not play a role in T antigen-induced dysplasia in the intestine. Furthermore, mice in which pRb was inactivated by a truncated T antigen in a p53 null background exhibited intestinal hyperplasia but no progression to dysplasia. In contrast, T antigen expression led to a large increase in the levels of the cyclin-dependent kinase inhibitor p21. We found that T antigen did not induce p53 stabilization, and we could not detect T antigen/p53 complexes in villus enterocytes. Therefore, we examined T antigen/p53 complexes from the intestines of transgenic mice. We hypothesized that the inhibition of the pRb family leads to entry of enterocytes into the cell cycle, resulting in hyperplasia, while inactivation of p53 is required for progression to dysplasia. Mice expressing a truncated T antigen that inactivates the pRb-family, but is defective for binding p53, exhibit hyperplasia but do not progress to dysplasia. Hyperplasia is dependent on T antigen binding to the retinoblastoma (pRb) family of tumor suppressor proteins. Transgenic mice expressing simian virus 40 large T antigen in enterocytes develop intestinal hyperplasia that progresses to dysplasia with age.
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