SIMILARITY BETWEEN NATURAL AND RECOMBINANT HUMAN ALPHA-FETOPROTEIN ASINHIBITORS OF ESTROGEN-DEPENDENT BREAST-CANCER GROWTH

Alpha-fetoprotein (AFP) isolated from rodent amniotic fluid or human c ord sera, upon incubation with a molar excess of estradiol, is convert ed to a form which inhibits estrogen-stimulated tissue growth. The pur pose of this study was to determine whether recombinant human AFP prod uced in an E. coli expression system retained this function. The recom binant protein was similar to the natural protein isolated from pooled human cord sera in all functional aspects evaluated. It was detected by monoclonal and polyclonal antibodies to the natural protein. Follow ing exposure to estradiol, it was converted to an inhibitor of estroge n-stimulated growth of immature mouse uterus yielding a dose/response curve similar to that of the natural protein. It inhibited the growth of estrogen-dependent (MCF-7) but not estrogen-independent (MDA-MB-231 ) breast cancer xenografts with the same schedule dependency and resul tant histological changes as the natural protein. Availability of larg e quantities of homogeneous, biologically active recombinant human AFP will facilitate further studies of structure/function, mechanism, and therapeutic potential of this agent as a regulator of breast cancer g rowth.