OXIDATIVE AND REDUCTIVE PATHWAYS OF ESTROGENS IN HORMONE-RESPONSIVE AND NONRESPONSIVE HUMAN BREAST-CANCER CELLS IN-VITRO

In order to measure the formation and degradation rates of estradiol b y human breast cancer cells, after assessing the biochemical basis of hormone responsiveness and growth response to estrogens, we considered both responsive, estrogen receptor (ER) positive, and non-responsive, ER-negative, breast cancer cell lines, i.e. MCF7, ZR75-1 and MDA-MB23 1. To this end, we employed a novel ''intact cell'' approach which all ows us, after 24 h incubation, to analyze several enzyme activities in sequence, concurrently with the monitoring of labeled precursor degra dation. Our investigations led to the following evidence: (a) the redu ctive activity of the 17 beta-hydroxysteroid oxoreductase (17 beta-HSO R) appears to be higher than the oxidative only in responsive, ER-rich MCF7 and ZR75-1 cells, as also previously observed by others; (b) thi s activity is, on the contrary, much lower in MDA-MB231 cells and othe r unresponsive, ER-poor breast cancer cell lines; (c) conversely, the oxidative activity shows an opposite pattern, being limited in MCF7 an d ZR75-1 cells and much higher in MDA-MB231 cells. Overall, a 17 beta- HSOR reductive pathway prevails in both MCF7 and ZR75-1 cells, whilst the oxidative pathway is prevalent in MDA-MB231 cells, leading to a la rge formation of estrone that is no further metabolized, at least in t he experimental conditions used. Our results may provide a likely expl anation of previous data on the different estrogen content of breast t umor tissues.