CHANGES IN THE PHOSPHORYLATION STATUS OF THE 27 KDA HEAT-SHOCK-PROTEIN (HSP27) ASSOCIATED WITH THE MODULATION OF GROWTH AND OR DIFFERENTIATION IN MCF-7 CELLS/
S. Horman et al., CHANGES IN THE PHOSPHORYLATION STATUS OF THE 27 KDA HEAT-SHOCK-PROTEIN (HSP27) ASSOCIATED WITH THE MODULATION OF GROWTH AND OR DIFFERENTIATION IN MCF-7 CELLS/, Cell proliferation, 30(1), 1997, pp. 21-35
We have used human mammary cells of the MCF-7 strain, which constituti
vely express high levels of the small heat shock protein HSP27 and we
have compared the changes in the phosphorylation status of this protei
n together with changes in cell growth and/or morphology induced by th
e action of one of the following agents: (1) TPA (12-O-tetradecanoylph
orbol-13-acetate), known as a differentiation inducer in MCF-7 cells;
(2) OH-TAM (hydroxytamoxifen), which exerts a cytostatic and cytotoxic
action; or (3) TNF chi (tumour necrosis factor), which induces apopto
tic cell death in this cell line. Our data show that TPA and TNF stimu
late an immediate and massive phosphorylation of HSP27, whereas OH-TAM
affect the phosphorylation status of the protein only after a 3 day d
elay. In the case of TPA, high levels of HSP27 phosphorylation were ma
intained for at least 4 days, along with growth inhibition and acquisi
tion by the cells of a secretory phenotype. TPA and OH-TAM exerted sim
ilar immediated effects on cell growth, despite the different time cou
rse of their action on HSP27 phosphorylation. This excludes the possib
ility that the latter is a necessary consequence of, or an absolute re
quisite to, growth inhibition. With OH-TAM and TNF the increase in HSP
27 phosphorylation was concomitant with the appearance of apoptosis, n
ot observed with TPA. This indicates that increased phosphorylation of
HSP27 is not specifically associated with the triggering or the execu
tion of apoptosis in these cells. Altogether, our data support the con
cept that phosphorylated HSP27 is involved (and might then be rate lim
iting in some instances) in the execution of vital cell programmes (in
cluding resistance to stress, proliferation and differentiation), as w
ell as in that of cell death. This is consistent with its role in acti
n polymerization and its position downstream of the p38/RK-type MAPkin
ase, itself a point of convergence for diverse signal transduction pat
hways.