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J Biol Chem, Vol. 273, Issue 25, 15345-15351, June 19, 1998
,
From the Life Science Group, During the exposure of human myelocytic leukemia
HL-60 cells to phorbol diester, nonadherent cells die by apoptosis, but
adherent cells survive and growth-arrest at G1 phase
of the cell cycle. Here we have shown that the adherent cells rapidly
died by apoptosis after forced detachment (anoikis), indicating that
phorbol diester induced apoptosis by default. Dimethylsphingosine
induced apoptosis in the adherent cells, and sphingosine-1-phosphate
rescued the detached cells from apoptosis. Sphingosine kinase activity
in adherent cells was higher than that in nonadherent cells and was decreased by forced detachment. It is likely that the phorbol diester-induced apoptosis and the adhesion-mediated survival are modulated by sphingosine and sphingosine-1-phosphate, respectively. The
adherent cells were reverted and reproliferated when allowed to
spontaneously detach from plastic surfaces by removal of phorbol diester. This result suggests that after removal of phorbol diester, the commitment signal of apoptosis by default is lost faster than the
survival signal by adherence.
Helix Research Institute,
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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