ALPHA-FETOPROTEIN DERIVED FROM A HUMAN HEPATOMA PREVENTS GROWTH OF ESTROGEN-DEPENDENT HUMAN BREAST-CANCER XENOGRAFTS

alpha-Fetoprotein (AFP) is a transport protein that has growth-regulat ory properties in many different tissues, It is known to interfere wit h responses stimulated by estrogen, The purpose of this study was to d etermine whether human AFP would inhibit the growth of human breast ca ncer, AFP was isolated from the culture supernatant of human hepatoma cells (HepG2) grown in serum-free medium and was purified by immunoaff inity chromatography. Human breast cancers were grown as xenografts un der the kidney capsule of severe combined immunodeficient mice. The mi nimum inhibitory dose of AFP against estradiol (E-2)-stimulated growth of human MCF-7 breast cancer xenografts was 10 mu g/mouse/day, and ma ximum inhibition (no growth) was achieved with 100 mu g/mouse/day. Dai ly treatment was required to sustain inhibition, This 100-mu g dose of AFP also inhibited xenograft growth of E-2-dependent T47 human breast carcinoma. Estrogen receptor-negative MDA MB 231 and BT20 human breas t carcinoma xenografts were not inhibited by AFP (100 mu g/mouse/day). Elevation in serum E-2 occurred during AFP treatment. AFP did not com pete with agonists for the estrogen receptor, These laboratory results are consistent with the findings of a literature search, which consis tently showed an association between elevated pregnancy levels of AFP and subsequent reduced risk for breast cancer later in life. We conclu de that AFP can inhibit growth of estrogen-dependent breast cancer and warrants further development as an agent for the treatment and perhap s even the prevention of human breast cancer.