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Similarity between natural and recombinant human alpha-fetoprotein as inhibitors of estrogen-dependent breast cancer growth

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Abstract

Alpha-fetoprotein (AFP) isolated from rodent amniotic fluid orhuman cord sera, upon incubation with a molarexcess of estradiol, is converted to a formwhich inhibits estrogen-stimulated tissue growth. The purpose ofthis study was to determine whether recombinant humanAFP produced in an E. coli expression systemretained this function. The recombinant protein was similarto the natural protein isolated from pooled humancord sera in all functional aspects evaluated. Itwas detected by monoclonal and polyclonal antibodies tothe natural protein. Following exposure to estradiol, itwas converted to an inhibitor of estrogen-stimulated growthof immature mouse uterus yielding a dose/response curvesimilar to that of the natural protein. Itinhibited the growth of estrogen-dependent (MCF-7) but notestrogen-independent (MDA-MB-231) breast cancer xenografts with the sameschedule dependency and resultant histological changes as thenatural protein. Availability of large quantities of homogeneous,biologically active recombinant human AFP will facilitate furtherstudies of structure/function, mechanism, and therapeutic potential ofthis agent as a regulator of breast cancergrowth.

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Authors and Affiliations

  1. Albany Medical College, Albany, New York, USA

    James A. Bennett & Herbert I. Jacobson

  2. McGill University, Montreal, Quebec, Canada

    Daniel J. Semeniuk & Robert A. Murgita

Authors
  1. James A. Bennett
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  2. Daniel J. Semeniuk
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  3. Herbert I. Jacobson
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  4. Robert A. Murgita
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Bennett, J.A., Semeniuk, D.J., Jacobson, H.I. et al. Similarity between natural and recombinant human alpha-fetoprotein as inhibitors of estrogen-dependent breast cancer growth. Breast Cancer Res Treat 45, 169–179 (1997). https://doi.org/10.1023/A:1005841032371

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