Activity and gene expression of 17beta-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

Abstract

17Beta-hydroxysteroid dehydrogenase (17-HSD) type I is present and active in most breast cancer cell lines where it modulates local estrogen availability. Currently no information is available on its expression in primary cultures. 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 breast. Regulation of 17-HSD type I by IL-8 in tumour-derived cultures was also studied. Reversible 17-HSD activity was observed in most samples. In cultures derived from normal breast, the oxidative pathway predominated by up to 51-fold in epithelial and 28-fold in stromal cells. In tumour-derived cultures, the reductive pathway predominated by up to 24-fold in epithelial and 20-fold in stromal cultures, with no preferred direction in the remaining samples. Expression of the 17-HSD type I gene was determined by quantitative RT-PCR. Although this was constitutively expressed by all samples from both tissue types, significantly higher levels of the gene were observed in tumour-derived cultures (P = 0.008, epithelial; P < 0.0001 stromal vs corresponding normal culture). IL-8 upregulated gene expression in epithelial cells 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 normal and tumourous breast and can be regulated by IL-8.