Document Detail


Response of small intestinal epithelial cells to acute disruption of cell division through CDC25 deletion.
MedLine Citation:
PMID:  19273838     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The CDC25 protein phosphatases (CDC25A, B, and C) drive cell cycle transitions by activating key components of the cell cycle engine. CDC25A and CDC25B are frequently overproduced in human cancers. Disruption of Cdc25B or Cdc25C individually or in combination has no effect on mouse viability. Here we report that CDC25A is the only family member to provide an essential function during early embryonic development, and that other family members compensate for its loss in adult mice. In contrast, conditional disruption of the entire family is lethal in adults due to a loss of small intestinal epithelial cell proliferation in crypts of Lieberkühn. Cdc25 loss induced Wnt signaling, and overall crypt structures were preserved. In the face of continuous Wnt signaling, nearly all crypt epithelial progenitors differentiated into multiple cell lineages, including crypt base columnar cells, a proposed stem cell. A small population of Musashi/Dcamkl-1/nuclear beta-catenin-positive epithelial cells was retained in these crypts. These findings have implications for the development of novel, less cytotoxic cancer chemotherapeutic drugs that specifically target the cell cycle.
Authors:
Gwanghee Lee; Lynn S White; Kristen E Hurov; Thaddeus S Stappenbeck; Helen Piwnica-Worms
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-03-09
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  106     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-03-25     Completed Date:  2009-04-08     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4701-6     Citation Subset:  IM    
Affiliation:
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blastocyst / cytology,  enzymology
Cell Division*
Cells, Cultured
Crosses, Genetic
Embryonic Development
Epithelial Cells / cytology*,  enzymology*,  ultrastructure
Female
G1 Phase
G2 Phase
Gene Deletion*
Genotype
Homeostasis
Intestine, Small / cytology*,  enzymology,  ultrastructure
Male
Mice
Mice, Knockout
cdc25 Phosphatases / deficiency*
Grant Support
ID/Acronym/Agency:
P30 CA91842/CA/NCI NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
EC 3.1.3.16/Cdc25a protein, mouse; EC 3.1.3.48/cdc25 Phosphatases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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