Bim is an apoptosis sensor that responds to loss of survival signals delivered by epidermal growth factor but not those provided by integrins.
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.
Wang
Pengbo
P
School of Biological Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom.
Gilmore
Andrew P
AP
Streuli
Charles H
CH
D000818:Animals; D023102:Anoikis; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology; D025461:Feedback, Physiological; D016023:Integrins / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D002352:Carrier Proteins; D016023:Integrins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D004815:Epidermal Growth Factor