Tamoxifen stimulates breast cancer growth following alteration of estroge...( Scientists have discovered that resista...)

Scientists have discovered that resistance to tamoxifen treatment can be mediated by a modification of the estrogen receptor. These results enhance the understanding of what underlies tamoxifen resistance in breast cancer and may eventually allow for earlier identification of resistant tumors, providing critical time to choose an alternative therapeutic strategy that is more likely to be effective.

Because nearly three-quarters of all breast cancers are stimulated by estrogen acting at functional estrogen receptors (ER+), they are most often treated with anti-estrogen compounds that inactivate the estrogen receptor. The most common of these is the drug tamoxifen. However, only about half of ER+ breast cancers successfully respond to treatment with tamoxifen, while the other half are resistant. When tamoxifen is used in advanced disease, resistance will eventually arise in all tumors, even if they were initially sensitive. It has been reported that tamoxifen-resistant breast tumors sometimes stop growing when tamoxifen is withdrawn. Dr. Rob Michalides and colleagues from the Department of Tumor Biology at The Netherlands Cancer Institute found that activation of the enzyme protein kinase A (PKA) induced tamoxifen resistance in breast cancer cells through a unique mechanism. PKA modified the estrogen receptor in such a way that although tamoxifen could still bind, it could no longer convert the receptor to an inactive form. Instead, it acted as an estrogen receptor activator and encouraged tamoxifen-resistant cancer cell growth. Using a genetic screening technique, the researchers showed that this mechanism was also operational in patients.

The findings indicate that PKA may be a critical determinant of how ER+ breast cancers respond to tamoxifen. "This is highly relevant for breast cancer patients, since tamoxifen might induce the opposite effect when PKA is activated, stimulating ER+ tumor growth instead of inhibiting it. Such pati
'"/>

Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
3-Jun-2004

Page: 1 2
Related biology news :

1. Tamoxifens effectiveness may be compromised by hot flash drug
2. Triple-vaccine strategy stimulates strong HIV-specific immune response in monkeys
3. Treatment stimulates growth and regeneration of injured adult skeletal muscle
4. Estrogen found in soy stimulates human breast-cancer cells in mice
5. Protein stimulates key link between nerve cells, suggesting possible target for mental retardation and nerve regeneration therapies
6. Study suggests ERT stimulates blood flow to key memory centers in brain
7. Protein that stimulates blood vessel growth also helps repair broken bones
8. Certain genes boost fish oils protection against breast cancer
9. Anti-cancer compound in vegetables found to block late-stage breast-cancer cell growth
10. Progress in breast cancer progression
11. The telomere crisis: A crucial stage in breast cancer