Estrogen Nuclear Receptor Coactivators in Pathogenesis of Breast Cancer

摘要

The success of anti-estrogen tamoxifen treatment of breast cancer and the discoveries that in a large number C breast tumors, proliferation of cells is stimulated by estrogen while retinoic acid exerts inhibitory effects have generated extensive interest among both clinicians and basic scientists. Presented studies have revealed a novel nuclear receptor coactivator of transcription referred to as p/CAF that is required for estrogen-, thyroid hormone and retinoic acid-dependent gene expression. DNA bound nuclear receptor directly recruits its coactivator p/CAF, and the association of p/CAF with a nuclear receptor depends upon ligand-dependent nuclear receptor corepressor (NCoR) dismissal. The critical role of the intrinsic acetyltransferase enzymatic activity of p/CAF in hormone regulated transcription provides a link between the function of this coactivator and steroid-dependent regulation of cell growth in pathogenesis of breast cancer. A substitution mutation eliminating acetyltransferase activity has been introduced into the p/CAF gene locus in order to examine biological function of this gene mouse. These studies have advanced our understanding of the molecular mechanism of hormone regulated gene expression and might open a new direction for improved treatment of breast cancer.