In vivo and in vitro expression of steroid-converting enzymes in human breast tumours: associations with interleukin-6

Enzymes modulating local steroid availability play an important role in the progression of human breast cancer. These include isoforms of 17 beta-hydr oxysteroid dehydrogenase (17-HSD), aromatase and steroid sulphatase (STS). The aim of this study was to investigate the expression, by reverse transcr iption polymerase chain reaction, of 17-HSD types I-IV, aromatase and stero id STS in a series of 51 human breast tumour biopsies and 22 primary cultur es of epithelial and stromal cells derived from these tumours, giving a pro file of the steroid-regulating network for individual tumours. Correlations between enzyme expression profiles and expression of the interleukin (IL)- 6 gene were also sought. All except one tumour expressed at least one isofo rm of 17-HSD, either alone or in combination with aromatase and STS. Expres sion of 17-HSD isoforms I-IV were observed in nine tumours. Of the 15 tumou rs which expressed three isoforms, a combination of 17-HSD II, III and IV w as most common (6/15 samples). The majority of tumours (n = 17) expressed t wo isoforms of 17-HSD with combinations of 17-HSD II and IV predominant (7/ 17 samples). Eight tumours expressed a single isoform and of these, 17-HSD I was in the majority (5/8 samples). In primary epithelial cultures, enzyme expression was ranked: HSD I (86%) > STS (77%) > HSD II (59%) > HSD IV (50 %) = aromatase (50%) > HSD III (32%). Incidence of enzyme expression was ge nerally reduced in stromal cultures which were ranked: HSD I (68%) > STS (6 7%) > aromatase (48%) > HSD II (43%) > HSD IV (28%) > HSD III (19%). Expres sion of IL-6 was associated with rumours that expressed greater than or equ al to 3 steroid-converting enzymes. These tumours were of higher grade and tended to come from patients with family history of breast cancer. In concl usion, we propose that these enzymes work in tandem with cytokines thereby providing sufficient quantities of bioactive oestrogen from less active pre cursors which stimulates tumour growth. (C)1999 Cancer Research Campaign.