Human serum albumin shares the properties of estrocolyone-I, the inhibitor of the proliferation of estrogen-target cells.
The control of cell proliferation by estrogens was examined under the premises of the indirect-negative hypothesis, which states that estradiol cancels the proliferative inhibition exerted by a serum-borne protein on estrogen-target cells. Fractionation protocols resulted in the co-elution of the inhibitory activity with serum albumin. Removal of human albumin (HA) from charcoal-dextran stripped serum by hexyl-S agarose 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 effect of HA. MCF-7 cells were exposed to recombinant human albumin (rHA) and to its rDomain I and rDomains I + II. Inhibition of proliferation was maximal with rHA and with rDomains I + II; rDomain I was less inhibitory. The inhibitory effect of albumin was cell type and protein specific. Only estrogens cancelled the albumin inhibition; recombinant growth factors and other hormones were ineffective. These data suggest that: (a) albumin or a portion of it (most likely within Domains I and II) is the specific inhibitory signal for the proliferation of human estrogen-target, serum-sensitive cells; (b) estrogens specifically cancel this inhibition; (c) inhibitory signals prevail over putative growth factors; and (d) the default state in these cells is proliferation.
Sonnenschein
C
C
Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
Soto
A M
AM
Michaelson
C L
CL
D001798:Blood Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D001943:Breast Neoplasms; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002846:Chromatography, Affinity; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D000077267:Fulvestrant; D006801:Humans; D007700:Kinetics; D015741:Metribolone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012709:Serum Albumin / Q000302:isolation & purification / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D001798:Blood Proteins; D004965:Estrogen Antagonists; D010446:Peptide Fragments; D011994:Recombinant Proteins; D012709:Serum Albumin; C079019:estrocolyone-I; D016222:Fibroblast Growth Factor 2; D000077267:Fulvestrant; D015741:Metribolone; D004958:Estradiol; D004815:Epidermal Growth Factor