Oestrogen-synthesising enzymes and breast cancer.
There is a large and compelling body of epidemiological and experimental evidence that oestrogens are the fuel behind the aetiology of breast cancer. The carcinogenic effects of oestrogen are postulated to be mediated by: the stimulation of cellular proliferation through their receptor-mediated hormonal activity. Other mechanisms include; direct genotoxic effects by increasing mutation rates through a cytochrome P450-mediated metabolic activation and induction of aneuploidy. The local biosynthesis of oestrogens, especially in postmenopausal women as a result of the interactions of various enzymes, is believed to play a very important role in the pathogenesis and development of hormone dependent breast carcinoma. The over-expression of such enzymes seems to be associated with the development of a more aggressive disease process, a poorer outcome and increased local and distant recurrences.
The London Breast Institute, The Princess Grace Hospitals, London, W1M 3FD, UK.
Myutan
M
Kulendran
Mohamed
M
Salhab
Kefah
K
Mokbel
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000737:chemistry / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004967:Estrogens / Q000096:biosynthesis*; D006801:Humans; D006836:Hydro-Lyases / Q000378:metabolism; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors / Q000378:metabolism
D004791:Enzyme Inhibitors; D004967:Estrogens; D015067:17-Hydroxysteroid Dehydrogenases; D001141:Aromatase; D043266:Steryl-Sulfatase; D006836:Hydro-Lyases