C. Sonnenschein et al., HUMAN SERUM-ALBUMIN SHARES THE PROPERTIES OF ESTROCOLYONE-I, THE INHIBITOR OF THE PROLIFERATION OF ESTROGEN-TARGET CELLS, Journal of steroid biochemistry and molecular biology, 59(2), 1996, pp. 147-154
The control of cell proliferation by estrogens was examined under the
premises of the indirect-negative hypothesis, which states that estrad
iol cancels the proliferative inhibition exerted by a serum-borne prot
ein on estrogen-target cells. Fractionation protocols resulted in the
co-elution of the inhibitory activity with serum albumin. Removal of h
uman albumin (HA) from charcoal-dextran stripped serum by hexyl-S agar
ose chromatography resulted in a preparation lacking inhibitory effect
. HA inhibited the proliferation of human estrogen-target MCF-7 cells.
Human non-estrogen-target MDA-MB231 cells were impervious to the effe
ct of HA. MCF-7 cells were exposed to recombinant human albumin (rHA)
and to its rDomain I and rDomains I + IT. Inhibition of proliferation
was maximal with rHA and with rDomains I + II; rDomain I was less inhi
bitory. The inhibitory effect of albumin was cell type and protein spe
cific. Only estrogens cancelled the albumin inhibition; recombinant gr
owth factors and other hormones were ineffective. These data suggest t
hat: (a) albumin or a portion of it (most likely within Domains I and
II) is the specific inhibitory signal for the proliferation of human e
strogen-target, serum-sensitive cells; (b) estrogens specifically canc
el this inhibition; (c) inhibitory signals prevail over putative growt
h factors; and (d) the default state in these cells is proliferation.
Copyright (C) 1996 Elsevier Science Ltd.