The Role Of Aromatase And Other Oestrogen Producing Enzymes In Mammary Carcinogenesis

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Mohamed Salhab and Kefah Mokbel

St. George's Hospital, London, SW17 0QT, UK

Abstract: There is a large and compelling body of epidemiological and experimental evidence that oestrogens are the fuel behind the aetiology of breast cancer. 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 and associated with poor outcome and increased local and distant recurrences. In this chapter we shed light on CYP19 gene expression, aromatase enzyme activity and its role in mammary carcinogenesis. In addition, other oestrogen producing enzymes such as 17beta hydroxy steroid dehydrogenase 1, 2 and steroid sulphatase and their role in breast cancer development are discussed in details. The understanding of the mechanisms that regulate these enzymes is crucial to the development of new endocrine preventa-tive and therapeutic strategies in postmenopausal females with hormone-dependant breast cancer. Currently, the third generation of aromatase inhibitors has revolutionised the treatment of oestrogen-dependant breast cancer. However, the important role of both STS and 17beta HSD type 1 in local oestrogen production provides novel potential targets for endocrine therapy. Such endocrine therapy is currently being explored and the development of STS inhibitors and 17beta HSD 1 inhibitors is underway with promising initial results.

Keywords: breast cancer, estrogen, postmenopausal, aromatase, 17beta HSD type 1, steroid sulphatase, carcinogenesis

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