Presence of alternatively spliced transcripts of aromatase gene in human breast cancer.

Abstract

The expression of aromatase (estrogen synthetase) is tissue specifically regulated through the alternative use of multiple exons 1 and promotors. We have determined the amounts of aromatase messenger ribonucleic acid (mRNA) and which type of multiple exons 1 of the human aromatase gene is used in breast tissues of 49 patients with breast cancer by reverse transcription-PCR analysis. The aromatase mRNA levels in these breast cancer tissues (4.53 +/- 0.66 x 10(-3) attomoles/micrograms RNA) were significantly (P < 0.01) higher than those in 16 nonmalignant breast tissues (1.73 +/- 0.40 x 10(-3) amol/micrograms RNA). Aromatase mRNA in all nonmalignant breast tissue were transcribed from skin fibroblast/fetal liver-specific exon 1 (exon 1b) of the gene. In 23 breast cancer tissues, the utilization of multiple exons 1 in the aromatase mRNA was the same as that in nonmalignant breast tissues, whereas in the other 26 cases, it changed from exon 1b to ovary-specific exon 1 (exon 1c). Such switching of tissue-specific exons 1 may affect strict regulation of the tissue-specific expression of aromatase, leading to abnormal expression of the aromatase. The consequent overproduction of local estrogen might promote carcinogenesis or the proliferation of breast cancers.