Selective activation of the glucocorticoid receptor by steroid antagonists in human breast cancer and osteosarcoma cells. Academic Article uri icon

Overview

abstract

  • Steroid hormones regulate the transcription of numerous genes via high affinity receptors that act in concert with chromatin remodeling complexes, coactivators and corepressors. We have compared the activities of a variety of glucocorticoid receptor (GR) antagonists in breast cancer and osteosarcoma cell lines engineered to stably maintain the mouse mammary tumor virus promoter. In both cell types, GR activation by dexamethasone occurs via the disruption of mouse mammary tumor virus chromatin structure and the recruitment of receptor coactivator proteins. However, when challenged with a variety of antagonists the GR displays differential ability to activate transcription within the two cell types. For the breast cancer cells, the antagonists fail to activate the promoter and do not promote the association of the GR with either remodeling or coactivator proteins. In contrast, in osteosarcoma cells, the antiglucocorticoids, RU486 and RU43044, exhibit partial agonist activity. The capacity of these antagonists to stimulate transcription in the osteosarcoma cells is reflected in the ability of the RU486-bound receptor to remodel chromatin and associate with chromatin-remodeling proteins. Similarly, the observation that the RU486-bound receptor does not fully activate transcription is consistent with its inability to recruit receptor coactivator proteins.

publication date

  • June 9, 2000

Research

keywords

  • Dexamethasone
  • Gene Expression Regulation, Neoplastic
  • Glucocorticoids
  • Hormone Antagonists
  • Hydroxycorticosteroids
  • Mammary Tumor Virus, Mouse
  • Mifepristone
  • Receptors, Glucocorticoid

Identity

Scopus Document Identifier

  • 0034625387

Digital Object Identifier (DOI)

  • 10.1074/jbc.M908729199

PubMed ID

  • 10748103

Additional Document Info

volume

  • 275

issue

  • 23