ESTROGEN REGULATION OF PROTOONCOGENES CODING FOR NUCLEAR PROTEINS

Estrogen hormones are known to exert a complex influence on developmen t and function of the female reproductive organs of vertebrates by reg ulating cell growth and differentiation, as well as to be implicated i n oncogenesis and maintenance of tumor growth. Estrogen acts on cells via interaction with an intracellular receptor, which, like all recept ors for steroid hormones, is a trans-acting transcription enhancer fac tor activated by the cognate ligand and capable of binding to specific , cis-acting enhancer elements usually located within the 5'-flanking regions of target genes. Additionally, estrogen regulates gene express ion by influencing mRNA stability or via interaction of the estrogen r eceptor with transcription regulatory factors. This article reviews da ta indicating that estrogen directly activates (primary activation) ex pression of proto-oncogenes codifying for nuclear proteins that, in tu rn, are responsible for indirect (secondary) activation of other genes . This cascade mechanism of gene activation is likely to progress for several more steps and allows us to envisage how estrogen can direct a complex task such as cell reproduction. Among proto-oncogenes codifyi ng for nuclear proteins, we focus on fos, jun, myc, and related genes. The mechanisms of regulation of these genes by estrogen, including re gulation of transcription, messenger RNA stabilization, and protein-pr otein interaction, are reviewed.