17-BETA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY IN ENDOMETRIAL CANCER-CELLS - DIFFERENT METABOLIC PATHWAYS OF ESTRADIOL IN HORMONE-RESPONSIVEAND NONRESPONSIVE INTACT-CELLS

In this paper we report that two human long-term endometrial cancer ce ll lines, Ishikawa and HEC-1A, exhibit quite different abilities in me tabolizing estrogens. As a matter of fact, incubation of Ishikawa cell s with close-to-physiological concentrations of estradiol (E(2)) as pr ecursor resulted in: (1) elevated formation (up to 90%) of E(2)-sulpha te (E(2)-S), using lower precursor concentrations; (2) very limited co nversion to estrone (E(1)) (<10% at 24 h incubation), as either free o r sulphate; and (3) low but consistent production of other estrogen de rivatives, such as 2-hydroxy-estrogens and estriol. Conversely, scant amounts (if any) of E(2)-S were found in HEC-1A cells, while no detect able formation of other estrogen metabolites could be observed after 2 4h. On the other hand, E(1) production was significantly greater (near ly 60% at 24 h) than in Ishikawa cells, a large proportion of E(1) (ov er 50% of the total) being formed after only 6 h incubation using time -course experiments. The hypothesis that E(2) metabolism could be mino r in Ishikawa cells as a consequence of the high rate of E(2)-S format ion encountered is contradicted by the evidence that conversion to E(1 ) also remains limited in the presence of much lower E(2)-S amounts, s een using higher molar concentrations of precursor. Overall, we observ e that 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity div erges significantly in intact Ishikawa and HEC-1A endometrial cancer c ells. This difference could not merely be accounted for by the diverse amounts of substrate (E(2)) available to the cells, nor may it be imp uted to different levels of endogenous estrogens. It should rather be sought in different mechanisms controlling 17 beta-HSD activity or, al ternatively, in the presence of distinct isoenzymes in the two differe nt cell types.