NDLI: Expression of wild-type and mutant simian virus 40 large tumor antigens in villus-associated enterocytes of transgenic mice.

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Expression of wild-type and mutant simian virus 40 large tumor antigens in villus-associated enterocytes of transgenic mice.

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Expression of wild-type and mutant simian virus 40 large tumor antigens in villus-associated enterocytes of transgenic mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Coopersmith, C. M. Kim, S. H. Roth, K. A. Gordon, J. I. Pipas, J. M.
Description	Author Affiliation: Kim SH ( Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110.);
Abstract	The four principal gut epithelial cell lineages undergo continuous and rapid renewal during a geographically well-organized migration along the crypt-to-villus axis. The molecules that regulate their proliferation and differentiation programs are largely unknown. The large tumor antigen (TAg) of wild-type (wt) simian virus 40 (SV40) and its mutant derivatives represent tools for describing the contributions of regulators of the cell cycle to the proliferative state of each lineage. Expression of SV40 TAgwt in postmitotic, villus-associated enterocytes of transgenic mice causes them to reenter the cell cycle without an apparent effect on their state of differentiation. When human KRAS with a Val-12 substitution ([Val12]KRAS) is coexpressed with SV40 TAgwt in villus enterocytes of bitransgenic animals, the two oncoproteins cooperate to produce dedifferentiation (dysplasia). SV40 mutant d11137 expresses a TAg that is unable to complex with p53 but retains N-terminal transforming functions, including the ability to complex pRB, p107, and p300. When SV40 TAgd11137 is expressed in villus enterocytes, they reenter into the cell cycle. However, coexpression of SV40 TAgd11137 and [Val12]KRAS does not produce dysplastic changes. Thus, the N-terminal 121 residues of TAg are sufficient to perturb the proliferative state of the enterocyte but not to produce detectable changes in the state of differentiation when coexpressed with [Val12]KRAS.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	15
Volume Number	91
Language	English
Publisher	National Academy of Sciences
Publisher Date	1994-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Polyomavirus Transforming Genetics Intestines Microbiology Animals Metabolism Cell Division DNA, Viral Mice Mice, Transgenic Microvilli Molecular Sequence Data Mutation Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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