The aromatase enzyme: from cloning to cancer

Abstract

Estrogen production by adipose tissue has been implicated in the etiology of such human cancers as endometrial and breast cancer. Estrogen production by adipose cells is subject to complex multifactorial regulation by a number of growth factors and cytokines, including those produced by breast cancer cells. In order to understand the mechanisms responsible for aromatase regulation, the structural gene encoding aromatase cytochrome P-450 (P-450AROM) was isolated from human genomic DNA. The gene spans at least 70 kb and is comprised of 10 exons, the first of which is untranslated. DNA sequence analysis indicates that the gene has a putative TATA (ATAAAA) sequence at -23 bp and putative CAAT binding sequences beginning at -41, -67, and -83 bp, that constitute a promoter region responsible for expression in placenta. However, this promoter does not appear to be responsible for expression in adipose, which may therefore be under the control of another, tissue-specific, promoter. Use of Polymerase Chain Reaction (PCR) technology has allowed for determination of expression of P-450AROM in samples of breast adipose. Preliminary results indicate that expression is highest in the upper lateral region, similar to the site of most frequent localization of tumors.