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 in tumour growth. To evaluate whether aromatase cytochrome P450 (P450arom) transcript levels within breast tumours were correlated to the enzyme activity, a specific competitive reverse transcription-polymerase chain reaction (RT-PCR) was developed. In this reaction, a 32 base-deleted complementary RNA was used as internal standard. In vitro aromatase activity was measured by either the tritium release assay or characterization of oestrogen fractions. Results indicate that there is a positive correlation between P450arom transcript levels and enzyme activity, but the relationship does not reach statistical significance. Therefore, whereas aromatase mRNA quantification may be an option by which to monitor the potential of tumour to synthesize oestrogens, it will not accurately reflect enzyme activity in a minority of tumours. Preliminary evidence was obtained in a tumour with low enzyme activity and a high P450arom transcript level for the presence of an endogenous aromatase inhibitor. This study highlights the necessity to characterize factors involved in the regulation of aromatase activity in such tumours.
Sourdaine
P
P
Imperial Cancer Research Fund, Medical Oncology Unit, Western General Hospital, Edinburgh, U.K.
Mullen
P
P
White
R
R
Telford
J
J
Parker
M G
MG
Miller
W R
WR
D001141:Aromatase / Q000096:biosynthesis / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D018076:DNA, Complementary; D005260:Female; D006801:Humans; D007700:Kinetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic
D018076:DNA, Complementary; D012333:RNA, Messenger; D001141:Aromatase