Aromatase gene expression in adipose tissue: relationship to breast cancer

Recent studies have established that concentration gradients of aromatase expression occur within the breast, with the highest levels of expression occurring in sites proximal to a tumor. These variations in aromatase expression correlate with regional differences in the relative proportions of the histologic components of breast adipose tissue, in particular adipocytes and stromal cells, since regions containing the highest numbers of stromal cells are the sites of elevated aromatase transcript levels. Although the initiating events are unknown, it is proposed that, once neoplastic cells start to replicate, tumor growth will be promoted by locally increased estrogen levels. In turn, growth factors produced by the tumor in response to locally increased estrogen levels may further increase aromatase expression in the surrounding adipose tissue. Thus a positive feed-back loop is established in which locally-produced estrogens and tumor-derived growth factors act by paracrine and autocrine mechanisms to sustain the growth and development of the tumor. Further support for this concept is obtained from the observation that aromatase expression in breast adipose is regulated by enhancer elements that appear to respond positively to growth factors, in contrast to expression in granulosa cells, which is inhibited by growth factors.