V. Speirs et al., In vivo and in vitro expression of steroid-converting enzymes in human breast tumours: associations with interleukin-6, BR J CANC, 81(4), 1999, pp. 690-695
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.