Oestrone sulphatase activity in mammary tumours and the liver of N-nitrosomethylurea treated rats

Abstract

Summary Oestrone sulphatase may be an important means of production of intra-tumoural oestrogens in breast cancer cells. The N-nitrosomethylurea induced rat mammary tumours, which is a good model of human breast carcinoma, was utilised to examine the significance of intra-tumoural oestrone sulphatase levels. The particular fraction (100,000 g pellet) was prepared from both the liver and the tumour of NMU treated rats and assayed for sulphatase activity. (Segaloff, 1978;Kirschner, 1979). Plasma levels of oestrone and oestradiol in postmenopausal women are very low, however the oestrogen concentration in breast tumour tissues is an order of magnitude higher than in the plasma (Millington, 1975;Edery et al., 1981;Fishman et al., 1977;Thorsen et al., 1982;van Landeghem et al., 1985;Thijssen & Blankenstein, 1989), suggesting local intra-tumoural production of oestrogens in breast tumour cells from precursor substrates. A comparative study of intra-tumoural aromastase and oestrone sulphatase activities has demonstrated that the sulphatase appears to be at least ten times more active than the aromatase enzyme in the production of intra-tumoural oestrogens from their respective precursor substrates (Santner et al., 1984). Therefore the sulphatase pathway is likely to be an important means of local production of biologically active oestrogens in human breast carcinoma tissue.The N-nitrosomethylurea-induced mammary gland carcinoma in rat is a good model of human breast carcinoma (Gullino et al., 1975). It is a hormone dependent model that regresses on oophorectomy and responds to anti-endocrine agents (Williams et al., 1981;Wilkinson et al., 1986). When these mammary tumours are grown in soft agar, colony formation is stimulated by oestrone sulphate. This is accompanied by the conversion of oestrone sulphate to oestradiol (Santner et al., 1986). An in vivo study demonstrated that oestrone sulphate can stimulate the growth of NMU-induced mammary tumour in castrate animals (Santner et al., 1990). This tumour contains levels of oestrone sulphatase activity similar to human tumours (Santner et al., 1984). The The animals in the oestrogen-treated group were injected with oestradiol at a dose of 0. Ijg kg-' in 0.2 ml of 0.9% NaCl subcutaneously daily for 5 days every week of the experiment. The rats in the control groups were similarly injected with 0.2 ml of 0.9% NaCl on the same days. The experiment was terminated by sacrificing all animals after 4 weeks.