Analysis on switching of alternative exons 1 causing aberrant expression of estrogen synthetase

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We have shown that elevation of aromatase expression in the proximal regions to breast cancer tissues was significantly correlated with switching of tissue-specific exons 1 of human aromatase gene in these regions. To further investigate what causes elevation of the aromatase mRNA and switching from exon 1b to exon 1c in the transcription factors of the aromatase gene in human breast cancer tissues, the effects of various on the exoression levels and preference of alternative expns 1 were examined in cultured adipose stromal cells from breast tissues. The aromatase mRNA was transcribed from exon 1b in the stromal cells cultured in the presence of calf serum. However, deprivation of the serum induced rapid elevation of aromatase mRNA and switching of aromatase transcripts to exon 1c the cells. Aromatase mRNA in HepG2 cells as well as in non-malignant breast tissues was also transcribed from exon 1b.Then, the promoter region responsible for the exon 1b-specific utilization in HepG2 cells was examined by fluorometric promoter assay using a new reporter containing 4 major alternative exons 1 and promoters. The results suggested that transcriptional elements determining preferential utilization of exon 1b in the cells was located on the promoter region of exon 1b form -255 to -1145. We have also observed significant levels of immunoreactive aromatase proteins and aromatase mRNA in the bone and vascular tissues. As decreased levels of estrogen in these tissues are paid attention in connecion with causes of osteoporosis in bone tissues and arterial sclerosis in vascular tissues and aromatase mRNA in these tissues is transcribed from exon 1b, switching of alternative exons 1 of the aromatase gene might contribute to a part of causes in these diseases.