Estrogen sensitivity of normal human breast tissue in vivo and implanted into athymic nude mice: Analysis of the relationship between estrogen-induced proliferation and progesterone receptor expression
- Cite this article as:
- Clarke, R.B., Howell, A. & Anderson, E. Breast Cancer Res Treat (1997) 45: 121. doi:10.1023/A:1005805831460
High serum concentrations of estradiol (E2) equivalent tothose observed in the luteal phase of the menstrual cycle stimulate bothepithelial cell proliferation and progesterone receptor (PgR) expression innormal human breast tissue xenografted into athymic nude mice. We reporthere the results of further investigations designed to determine whether theinduction of PgR expression and proliferation require differentE2 concentrations and whether proliferating cells expressedthe PgR. In untreated normal breast xenografts, the PgR was virtuallyundetectable and proliferation was at basal levels. Progesterone (Pg)treatment alone had no effect compared to no treatment. Treatment withE2 at follicular phase serum concentrations maximallyincreased PgR expression but was without effect on proliferation. However,treatment with E2 at luteal phase serum concentrations, aloneor in combination with Pg, significantly increased both the PgR content andthe proliferation of the breast epithelium. These experimentally deriveddata reflected the observations made on normal breast tissue at surgicalbiopsy where PgR content was similar in both halves of the menstrual cycle,whereas proliferation was significantly higher in the luteal phase. Finally,using double labelling techniques, it was demonstrated that proliferatingepithelial cells rarely expressed PgR in normal breast tissue obtained atsurgical biopsy. These results suggest that the threshold ofE2 required to induce PgR expression in normal human breastepithelial cells is lower than that required to induce proliferation andthat the majority of proliferating breast cells do not express the PgR.