Santen, “In situ aromatization enhances breast tumor estradiol levels and cellular proliferation

The high concentrations of estradiol i!•'.,i found in breast tumors of postmenopausal women could be the result of enhanced uptake from plasma or in situ aromatization of androgens to estrogens. To test the relative importance of these two mechanisms, a model system allowing precise distinction between each is required. Such a model was established using aromatase (A +)- and sham (A-)-transfected MCF-7 cells inocu lated into ovariectomized lOVXi nude mice. To validate the model, the confounding effect of peripheral aromatization was first excluded exper imentally. A—cells were inoculated into OVX mice as homoimplants (A —¿ cells on both flanks) or heteroimplants (A- cells on one flank and A + cells on the other), and growth of A—cells in response to exogenous aromatase substrate, androstenedione (A4A), was evaluated. A- cells did not grow in either group during the 8 weeks of observation, indicating the lack of peripheral aromatization in OVX mice. The biological effects of i