EXPRESSION OF CYTOSOLIC SULFOTRANSFERASES IN NORMAL MAMMARY EPITHELIAL-CELLS AND BREAST-CANCER CELL-LINES

Breast cancers require the presence of estrogens for the maintenance o f growth at some time in the course of their development, as does norm al breast tissue. Sulfation is an important process in the metabolism and inactivation of steroids, including estrogens, because the additio n of the charged sulfonate group prevents the binding of the steroid t o its receptor. Also, many of the therapeutic and chemopreventive agen ts used in the treatment of breast cancer are substrates for the sulfo transferases (STs). The activity and expression of four cytosolic STs, which are the human phenol-sulfating and monoamine-sulfating forms of phenol ST (PST), dehydroepiandrosterone ST, and estrogen ST (hEST), w ere assayed in normal breast cells and in breast cancer cell lines, ST activities and immunoreactivities were assayed in the estrogen recept or-positive human breast cancer cell lines ZR-75-1, T-47D, and MCF-7; in the estrogen receptor-negative breast cancer cell lines BT-20, MDA- MB-468, and MDA-MB-231; and in normal human mammary epithelial cells. The PSTs were the most highly expressed ST activities in the breast ca ncer cell lines, although the Levels of activity varied significantly, ZR-75-1 and BT-20 cells possessed the highest levels of activity of t he human phenol-sulfating form of PST. The breast cancer cell lines sh owed only trace levels of dehydroepiandrosterone ST and hEST activitie s. In contrast, hEST was the only ST detectable in human mammary epith elial cells. Understanding the regulation of ST activity in these brea st cancer and normal breast cell lines will improve our knowledge of t he role of sulfation in breast cancer and provide a model with which t o study the mechanism of action of estrogens in mammary cells.