Identification of Genes Differentially Regulated by Progestins and Glucocorticoids in Human Breast Cancer Cells.

摘要

Glucocorticoids and progestins bind to receptors that share many structural and functional similarities. Nonetheless, they mediate district biological functions. Progestins are associated with the incidence and progression of breast cancer, whereas glucocorticoids are growth suppressive in mammary cancer cells. To understand the mechanisms that engender biological specificity, we have employed two systematic approaches to identify genes that are differentially regulated by the two hormones. The first approach is a retroviral promoter-trap, which allowed the identification of two novel genes that are differentially regulated as well as another novel gene induced by both hormones. The second strategy is to utilize Affymetrix microarrays to compare glucocorticoid- and progestin- regulated gene expression in a human breast cancer cell line. This global analysis reveals that the two hormones regulate overlapping but distinct sets of genes, including 31 genes that are differentially regulated. Examination of the set of differentially regulated genes suggests mechanisms behind the distinct growth effects of the two hormones in breast cancer. The differential regulation of four genes was confirmed by RT- PCR and northern blot analyses. Detailed analyses of genes identified here will furnish a mechanistic understanding of differential gene regulation by glucocorticoids and progestins in breast cancer.