Cell Cycle Regulation of Estrogen and Androgen Receptor
Annual summary rept. 1 Jul 2000-30 Jun 2001
GEORGETOWN UNIV WASHINGTON DC MEDICAL CENTER
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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 G1S boundary. Androgen upregulation of receptor protein is seen in both G0 and G1S 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.
- Anatomy and Physiology
- Medicine and Medical Research