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    Damage-induced apoptosis in intestinal epithelia from bcl-2-null and bax-null mice: investigations of the mechanistic determinants of epithelial apoptosis in vivo.

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    Authors
    Pritchard, D Mark
    Potten, Christopher S
    Korsmeyer, Stanley J
    Roberts, Stephen A
    Hickman, John A
    Affiliation
    CRC Molecular and Cellular Pharmacology Group, School of Biological Sciences, Stopford Building (G38), University of Manchester, Manchester M13 9PT, UK.
    Issue Date
    1999-12-02
    
    Metadata
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    Abstract
    The influence of bcl-2 and bax expression on apoptotic cell death in mouse intestinal epithelia was assessed using homozygously null mice. Apoptosis was induced in vivo by the enterotoxin 5-fluorouracil (5FU) or by gamma-irradiation and its cell positional incidence was assessed. 5FU and gamma-radiation treated bax-null mice surprisingly showed no reductions in apoptotic yield in the small intestine or midcolon at 4.5 h at cell positions in which both agents had previously been shown to strongly induce p53 protein expression. The colonic epithelia of 5FU treated bcl-2-null mice showed elevated levels of apoptosis at 4.5 h: from 48 apoptotic events in wild-type mice to 273 in the nulls, scoring 200 half crypts. The increase occurred specifically in the cell positions considered to harbour colonic stem cells, at the base of crypts, where there is selective expression of bcl-2. There was a modest but significant increase in apoptosis in the small intestine of the bcl-2-null mice although the epithelia of wild-type mice here are not immunohistochemically positive for bcl-2 protein. These findings show that bcl-2 plays a key role in determining the sensitivity of colonic stem cells to damage-induced death but that bax is not responsible for the p53-dependent induction of apoptosis in this context.
    Citation
    Damage-induced apoptosis in intestinal epithelia from bcl-2-null and bax-null mice: investigations of the mechanistic determinants of epithelial apoptosis in vivo. 1999, 18 (51):7287-93 Oncogene
    Journal
    Oncogene
    URI
    http://hdl.handle.net/10541/91341
    DOI
    10.1038/sj.onc.1203150
    PubMed ID
    10602483
    Type
    Article
    Language
    en
    ISSN
    0950-9232
    ae974a485f413a2113503eed53cd6c53
    10.1038/sj.onc.1203150
    Scopus Count
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    All Paterson Institute for Cancer Research

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