Hormonal steroids act as tumour promoters by modulating oncogene expression

Abstract

Recent advances in the molecular action of steroid hormones and in the role of oncogenes in cell transformation are considered in defining, at the molecular level, the involvement of steroid hormones in tumour formation. In the context of the generally accepted three-stage model of carcinogenesis, it is proposed that the hormonal steroids act as tumour promoters by modulating oncogene expression. It is postulated that the hormonal steroids act on cells in which the initiating carcinogen has either induced mutations in protooncogenes normally hormonally regulated or has induced changes in gene architecture, aligning protooncogenes to hormone-responsive elements, thus placing these genes under non-physiological hormonal control. In contrast to the defined action of solitary carcinogens on the genetic material, tumour promoters appear to act by various molecular pathways, one of which, as hypothesized for hormonal steroids, could be a direct effect on oncogene expression.