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Oestrogen sulphatase activity in hormone‐dependent and hormone‐independent breast‐cancer cells: Modulation by steroidal and non‐steroidal therapeutic agents
Author(s) -
Purohit A.,
Reed M. J.
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910500614
Subject(s) - medicine , endocrinology , tamoxifen , steroid sulfatase , chemistry , cell culture , danazol , intracellular , hormone , estrogen , steroid , biology , breast cancer , cancer , biochemistry , endometriosis , genetics
Oestrogen sulphatase may play an important role in providing intracellular oestrogens from E 1 S for the growth and maintenance of breast tumours. In this study, we characterized oestrogen sulphatase in the hormone‐dependent (ER/PR + ) MCF‐7 and in the hormone‐independent (ER/PR ) MDA‐MB‐231 breast‐cancer cells and, furthermore, examined its modulation by MPA, 4‐OH‐A 4 , tamoxifen, danazol, ethinyloestradiol and DMAS in both these cell types. Our detailed study of oestrogen sulphatase activity as a function of incubation time, E 1 S concentration and numbers of MCF‐7 and MDA‐MB‐231 cells showed that more E 1 S was hydrolysed by MDA‐MB‐231 cells than by MCF‐7 cells at all time points and all substrate concentrations. Additionally, although the k m values of E 1 S for oestrogen sulphatase in both MCF‐7 and MDA‐MB‐231 cells were similar, the V max values, and therefore the activity, differed greatly. The effect of various steroidal and non‐steroidal compounds also suggested differences in these 2 cell lines with respect to oestrogen sulphatase inhibition or stimulation. MPA significantly increased the hydrolysis of [ 3 H]E 1 S in both cell lines, possibly through its effect on membrane fluidity. Tamoxifen increased E 1 S hydrolysis in MDA‐MB‐231 cells but not in MCF‐7 cells, whereas 4‐OH‐A 4 inhibited E 1 S in MCF‐7 cells but not in MDA‐MB‐231 cells. Danazol (an isoxazol derivative of 17α‐ethinyltestosterone), 17α‐ethinyloestradiol and DMAS all significantly inhibited oestrogen sulphatase activity in both cell lines. Furthermore, danazol had a growth‐inhibitory effect on both MCF‐7 and MDA‐MB‐231 cells, although MCF‐7 cells appeared to be more sensitive to growth inhibition by danazol.