HORMONE-INDUCED DUCTAL DNA-SYNTHESIS OF HUMAN-BREAST TISSUES MAINTAINED IN THE ATHYMIC NUDE-MOUSE

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  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (9) , 3300-3305
Abstract
Five biopsy specimens of morphologically normal human breast tissues obtained from the margins of 5 benign human breast tumors were processed into slices (4.0 .times. 4.0 .times. 0.1 mm) and transplanted s.c. dorsally (8-10 slices/mouse) into 43, 6- to 8 wk old female BALB/c, athymic nude mice. Each individual tissue specimen was transplanted into 7-10 mice. After 30 days the mice were divided into 4 groups and treated for 30 days as follows: cholesterol pellets administered s.c. to controls; estrogens administered in s.c. pellets containing 2 mg 17.beta.-estradiol and 38 mg cholesterol and in drinking water containing 0.5 mg estrone/l; rat pituitary tumor (RPT), a cell suspension of MtT-W10 RPT that secretes large amounts of prolactin and growth hormone, injected dorsorostrally; and RPT plus estrogens. Three to five human breast tissue grafts were removed from each mouse at the onset of treatment and the remainder were removed at termination of treatment. DNA synthesis in the ductal epithelium was determined in pre- and posttreatment grafts by [3H]thymidine autoradiography after incubation of grafts for 4 h in an isotope-enriched medium. The labeling index (LI), mean number of labeled epithelial cells per unit area of epithelial tissue in pre- and posttreatment grafts was, respectively: control, 7.6 .+-. 1.4 and 7.1 .+-. 1.4; estrogens, 5.5 .+-. 0.6 and 17.9 .+-. 2.3; RPT, 6.2 .+-. 0.7 and 8.0 .+-. 1.5; and RPT plus estrogens, 6.3 .+-. 0.8 and 26.6 .+-. 2.5. A significant increase in LI was observed after treatment with estrogens (P < 0.01) or RPT plus estrogen (P < 0.001). Mean LI after treatment with RPT plus estrogens was significantly greater (P < 0.02) than after estrogens alone. RPT alone did not significantly alter the LI. Estrogens apparently enhance DNA synthesis of the ductal epithelium of the normal human breast and a growth factor (or factors) from RPT acts synergistically with estrogens to produce a more pronounced increase in DNA synthesis. RPT growth factors (perhaps prolactin and/or growth hormone) appear to require estrogens for DNA synthesis stimulation in normal human breast ductal epithelium.