Reconstituted normal human breast in nude mice: estrogen and progesterone receptors regulation

Actions of estrogen and progesterone on normal human breast are mediated by their respective receptors. Since receptor regulation studies in humans are difficult to perform, we have utilized our model system of reconstituted normal human breast in nude mice to determine expression of estrogen and progesterone receptors in response to exogenous estrogen and progesterone. In normal human breast in situ, only a subset of epithelial cells (about 10%) are positive for estrogen receptor. These cells which remain positive after transplantation into nude mice can be completely downregulated by administration of exogenous estrogen resulting in all transplanted human breast epithelial cells now being negative for estrogen receptor. Exogenous estrogen also upregulates the progesterone receptor in a subset of human breast epithelial cells rather than in all cells. Exogenous progesterone, alone or in combination with estrogen, did not affect the estrogen or progesterone receptors. Double immunofluorescent labelings for a proliferation marker and progesterone receptor in both surgical specimens and nude mice transplants demonstrate that proliferation and progesterone receptor expression do not take place in the same cell. Our in vivo model system enables studies on the biology of primary normal human breast epithelial cells which otherwise are difficult to perform in humans.