The Identification of Genes Differentially Regulated by Progestins and Glucorticoids in Human Breast Cancer Cells
Annual summary 1 Jul 2000-30 Jun 2001
COLORADO UNIV HEALTH SCIENCES CENTER DENVER
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Progestins and glucocorticoids are two classes of steroid hormone with very distinct biological functions. Progestins have been shown to relate to the incidence and progression of breast cancer, but glucocorticoids have no direct relation with breast cancer to our knowledge. However, progesterone receptor and glucocorticoid receptor share many structural and functional similarities including identical DNA sequence recognition characteristics. To understand the role of progestins in breast cancer and how progesterone receptor mediates this hormone specific regulation, we identified genes that are differentially regulated by progestins and glucocorticoids using two systematic strategies a retroviral promoter-trapping strategy and an oligonucleotide array analysis. The retroviral promoter-trapping system allowed the identification of two novel genes that are differentially regulated. Another novel gene was identified to be induced by both hormones. The Affymetrix microarray analysis allowed the identification of 42 differentially regulated genes in the human breast cancer cells T47DA1-2. Confirmation of the expression pattern of all four genes selected with RT-PCR and Northern blot analysis demonstrated the reliability of the array results. Studies of the mechanisms underlying the expression pattern of these genes identified will help us to understand hormone-specific actions and the role of progestins in breast cancer.
- Medicine and Medical Research