Oestrone sulphatase activity in mammary tumours and the liver of N-nitrosomethylurea treated rats.
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. The tumour enzyme had an optimum pH of 7.2, Km value of 14.8 microM and Vmax of 0.90 nmoles min-1 mg-1, while the hepatic enzyme was optimal at pH 7.4, Km of 10.8 microM and Vmax of 3.71 nmoles min-1 mg-1. The relationship of intra-tumoural sulphatase levels with tumour regression and progression in endocrine responsive tumours was investigated. Tumour regression as a result of oophorectomy was associated with a significantly decreased intra-tumoural sulphatase level (mean level = 0.165 nmoles min-1 mg-1) in comparison to a control group (mean level = 0.319 nmoles min-1 mg-1, P less than 0.05) in which the tumours remained stable. This significant difference was not observed in the corresponding hepatic samples suggesting that it is the intra-tumoural rather than the peripheral production of oestrogens by oestrone sulphatase that is important in supporting growth of endocrine responsive tumours.
Evans
T R
TR
CRC Department of Medicine Oncology, Charing Cross Hospital, UK.
Chander
S K
SK
Rowlands
M G
MG
Coombes
R C
RC
D000818:Animals; D003600:Cytosol / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D008770:Methylnitrosourea / Q000633:toxicity*; D010052:Ovariectomy; D051381:Rats; D011919:Rats, Inbred Strains; D013429:Sulfatases / Q000378:metabolism*
D004958:Estradiol; D008770:Methylnitrosourea; D013429:Sulfatases; C020121:estrone sulfatase