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J. Biol. Chem., Vol. 279, Issue 40, 41280-41285, October 1, 2004
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From the School of Biological Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom
Anoikis is a rapid apoptosis response that is initiated within a few minutes after inhibition of integrin signaling. In mammary epithelia, anoikis is mediated by subcellular translocation of Bax from the cytosol to mitochondria where it activates the intrinsic apoptosis pathway. The Bcl-2 homology 3 domain-only protein, Bim, has been proposed to have a key role in the apoptosis response of an epithelial cell line with reduced sensitivity to loss of integrin signaling, which undergoes apoptosis over a period of several days in suspension culture. Here we tested the involvement of Bim in the rapid anoikis response of mouse mammary epithelial cells and discovered that Bim does not have a role in detecting integrin-mediated signals. Instead Bim senses the loss of survival cues mediated by epidermal growth factor. Cell lines selected over many passages in culture have lost much of their sensitivity to anoikis signals arising from an altered cellular microenvironment and may undergo apoptosis through acquired mechanisms.
Received for publication, May 28, 2004 , and in revised form, July 13, 2004.
* This work was supported by The Wellcome Trust and the Medical Research Council. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
To whom correspondence should be addressed: School of Biological Sciences, University of Manchester, Oxford Rd., Manchester M13 9PT, UK. Tel.: 44-161-275-5626; Fax: 44-161-275-1505; E-mail: cstreuli{at}man.ac.uk.
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