Cell Cycle Regulation of Estrogen and Androgen Receptor
Abstract
We seek to identify the phases in the cell cycle during which steroid-activated estrogen and androgen receptors are normally transcriptionally active and to determine whether this regulation is maintained by cancer-inducing non-steroidal agents. We have found that the androgen receptor (AR) has optimal activity in G0 cells. The receptor shows moderate activity in cells along S phase. However, it has been found that the AR losses its activity at the G1/S boundary. Androgen upregulation of receptor protein is seen in both G0 and G1/S arrested cells, although the final receptor levels are consistently higher in G0 cells. Serum starved cells consistently show 10-20 fold induction of estrong receptor activity. Treatment with hydroxyurea after starvation obliterated all ER activity while the same drug treatment on asynchronous cells reduced estrogen activation to 3-4 fold over basal values. Hydroxyurea treatment of serum starved cells had only a slight effect on estrogen activity. Non-steroidal activators tested with our cells induced ER or AR two or three fold or not at all. Through these studies we are gaining understanding of how estrogen and androgen receptors are regulated and how their deregulation may contribute to the onset of tumorigenesis and hormone independent growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADB275662
Entities
People
- Elisabeth D. MartÃnez
Organizations
- Georgetown University