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Aromatase cytochrome P450 expression and activity levels in benign and malignant human breast tissue

Aitken, Jane; (1993) Aromatase cytochrome P450 expression and activity levels in benign and malignant human breast tissue. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Aromatase cytochrome P450 is the final enzyme in the steroidogenic pathway from the C-19 androgens to the C-18 oestrogens. This enzyme is located in a number of tissues throughout the body, including breast adipose tissue and breast carcinoma tissue. The importance of local aromatase activity in the breast is at the present time unknown. This thesis had studied the mRNA and activity levels of aromatase in adipose and tumour tissue collected from women undergoing surgery for benign or malignant breast disease. Aromatase activity was measured using the tritiated water release assay and the mRNA levels quantified using a novel Polymerase Chain Reaction Technique. All samples of benign lesion tissue were found to contain the mRNA encoding aromatase and 70% of the samples had detectable amounts of aromatase activity in either the lesion or adipose tissue. There were no significant correlations between aromatase activity in either tissue with a variety of clinical indices, except that aromatase activity in the adipose tissue of those patients who reported a negative family history of breast cancer was higher than those patients with a positive family history. 134 patients with malignant breast disease were studied, 82.6% were found to have mRNA encoding aromatase in the carcinoma and 81.9% had detectable aromatase activity in the carcinoma. The aromatase activity levels in both the carcinoma and adipose tissue were compared to various clinical indices and it was found that aromatase activity in the carcinoma was inversely related to both age at menopause and oestrogen receptor concentration. There was no correlation between aromatase activity in the adipose tissue and location of the cancer in 65 patients. However, in a separate group of 19 patients there was a significant correlation between aromatase mRNA levels in the adipose and location of the cancer, the highest levels being in the adipose tissue of the cancer bearing quadrant. There were no correlations between the mRNA levels and aromatase activity in the carcinomas or any of the clinical indices. It would appear that the carcinomas may be able to regulate their maintenance and/or growth via localised oestrogen production utilising the aromatase enzyme.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Aromatase cytochrome P450 expression and activity levels in benign and malignant human breast tissue
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10106959
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