Activity and gene expression of 17 beta-hydroxysteroid dehydrogenase type I in primary cultures of epithelial and stromal cells derived from normal and tumourous human breast tissue: The role of IL-8

17 beta-hydroxysteroid dehydrogenase (17-HSD) type I is present and active in most breast cancer cell lines where it modulates local estrogen availabi lity. Currently no information is available on its expression in primary cu ltures. We have quantitatively determined the cellular localisation of both enzyme activity and expression of the 17-HSD type I gene using a series of primary epithelial and stromal cells derived from normal and tumourous bre ast. Regulation of 17-HSD type I by IL-8 in tumour-derived cultures was als o studied. Reversible 17-HSD activity was observed in most samples. In cult ures derived from normal breast, the oxidative pathway predominated by up t o 51-fold in epithelial and 28-fold in stromal cells. In tumour-derived cul tures, the reductive pathway predominated by up to 24-fold in epithelial an d 20-fold in stromal cultures, with no preferred direction in the remaining samples. Expression of the 17-HSD type I gene was determined by quantitati ve RT-PCR. Although this was constitutively expressed by all samples from b oth tissue types, significantly higher levels of the gene were observed in tumour-derived cultures (P = 0.008, epithelial; P < 0.0001 stromal vs corre sponding normal culture). IL-8 upregulated gene expression in epithelial ce lls but it was downregulated in stroma. This was reflected in 17-HSD type I activity. Thus, 17-HSD type I is constitutively expressed and active in no rmal and tumourous breast and can be regulated by IL-8. (C) 1998 Elsevier S cience Ltd. All rights reserved.