AROMATASE-ACTIVITY AND CYP19 GENE-EXPRESSION IN BREAST CANCERS

The aromatase enzyme complex is responsible for the conversion of C19 androgens to oestrogens. Aromatase expression in oestrogen-responsive breast cancers may be an important mechanism of autocrine regulation i n tumour growth. To evaluate whether aromatase cytochrome P450 (P450ar om) transcript levels within breast tumours were correlated to the enz yme activity, a specific competitive reverse transcription-polymerase chain reaction (RT-PCR) was developed. In this reaction, a 32 base-del eted complementary RNA was used as internal standard. In vitro aromata se activity was measured by either the tritium release assay or charac terization of oestrogen fractions. Results indicate that there is a po sitive correlation between P450arom transcript levels and enzyme activ ity, but the relationship does not reach statistical significance. The refore, whereas aromatase mRNA quantification may be an option by whic h to monitor the potential of tumour to synthesize oestrogens, it will not accurately reflect enzyme activity in a minority of tumours. Prel iminary evidence was obtained in a tumour with low enzyme activity and a high P450arom transcript level for the presence of an endogenous ar omatase inhibitor. This study highlights the necessity to characterize factors involved in the regulation of aromatase activity in such tumo urs. Copyright (C) 1996 Elsevier Science Ltd.