CYP19 (AROMATASE CYTOCHROME-P450) GENE-EXPRESSION IN HUMAN-MALIGNANT ENDOMETRIAL TUMORS

C-19 steroids are converted to estrogens in a number of human tissues by the aromatase enzyme complex, which consists of aromatase cytochrome P450 (P450arom; product of the CYP19 gene) and NADPH-cytochrome P450 reductase. Aromatase activity has been previously demonstrated in endometrial tumors. In the present study, we investigated CYP19 gene expression and its regulation in endometrial tumor samples (n = 9). Using a specific method of competitive polymerase chain reaction after reverse transcription, varying levels of P450arom transcripts were detected in all endometrial adenocarcinomas (n = 8) and one mixed Mullerian tumor studied. No correlations were observed between P450arom transcript levels and histological type of the tumor, grade, myometrial invasion; stage of the disease, or patient age. We have recently demonstrated that the tissue-specific regulation of CYP19 gene transcription is in part the consequence of alternative promoter use. The use of each promoter gives rise to a P450arom transcript with a unique untranslated 5'-end. We analyzed the untranslated first exons in 5'-terminals of P450arom transcripts in endometrial adenocarcinomas using a specific reverse transcription-polymerase chain reaction/Southern hybridization method we recently developed. Our findings indicated the gonadal-type (promoter II) and one of the adipose stromal cell-type (I.3) promoters were primarily used for P450arom expression in adenocarcinomas. On the other hand, distribution of transcripts specific for I.3, I.4 (another adipose-type promoter), and promoter II in one mixed Mullerian tumor was uniform. Placental promoter (I.1)-specific P450arom transcripts were not detected in endometrial tumors. As P450arom transcripts were detected in all endometrial malignancies studied, whereas they were not demonstrable in the disease-free endometrium, activation or failure of inhibition of aromatase expression in these tumors may serve to promote neoplastic proliferation.