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

Abstract

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.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2002
Accession Number
ADA406196

Entities

People

  • Steven K. Nordeen
  • Yihong Wan

Organizations

  • University of Colorado Health

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Carrier Proteins
  • Cell Line
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Dna Microarrays
  • Gene Expression
  • Genetic Structures
  • Genetics
  • Growth Factors
  • Identification
  • Microarray Analysis
  • Molecular Dynamics
  • Neoplasms
  • Peptides
  • Proteins

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular Genetics