Navigation Links
Unsuspected protein determines resistance to breast cancer treatment
Date:2/4/2008

An innovative research approach has identified a previously unsuspected protein as a key player in the resistance to particular forms of breast cancer therapy. The study, published by Cell Press in the February issue of Cancer Cell, significantly advances the understanding of the molecular response to breast cancer therapies that target estrogen signaling.

Most breast tumors express estrogen receptor and are dependent on estrogen signaling. Drugs that target this characteristic, such as tamoxifen, have had a major impact on breast cancer therapy as they interfere with the ability of estrogen to activate its receptor and, as a result, limit cellular proliferation.

However, although widely used, the effectiveness of tamoxifen is profoundly limited by the development of drug resistance. All patients with metastatic disease and 40% of early-stage breast cancer patients treated with tamoxifen eventually relapse with tamoxifen-resistant disease, explains lead author Professor Alan Ashworth from the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research in London, England.

To develop a better understanding of the molecular events that contribute to the development of treatment resistance, Prof. Ashworth, Dr. Christopher J. Lord and colleagues used a sophisticated and highly selective loss-of-function RNA interference screening method to identify genes that, when silenced, cause tamoxifen resistance. The researchers identified Cyclin-Dependent Kinase 10 (CDK10) as a critical component of the response to tamoxifen and other therapies that target estrogen signaling.

Examination of signaling molecules downstream of CDK10 led the authors to propose that CDK10 normally represses the ETS2 transcription factor and that the loss of CDK10 expression results in relief of ETS2 repression and upregulation of c-RAF transcription. Enhanced c-RAF activation results in activation of mitogen-activated protein kinase and increased cyclin D1 expression, both previously linked to tamoxifen resistance. Together, these events link tamoxifen with a loss of reliance on estrogen signaling.

Importantly, the researchers also found that in patients treated with tamoxifen, drug resistance occurred significantly earlier in those with tumors that express low levels of CDK10. Furthermore, methylation of the CDK10 gene also correlated with resistance. Methylation of genes is well-established as a means by which gene expression can be controlled and suggests a mechanism that could switch off CDK10 expression in tumor cells.

Drug resistance is a serious problem for women with breast cancer. Its devastating for a patient to see their cancer return because of resistance, especially after enduring a long course of treatment and after a long period of remission. Through this work, weve identified some of the factors that control this effect and in the future we may be able to use this information to decide which treatments to give to patients to avoid resistance, says Prof. Ashworth.


'/>"/>

Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

Related medicine news :

1. Draining away brains toxic protein to stop Alzheimers
2. Penn study finds pro-death proteins required to regulate healthy immune function
3. New prion protein discovered by Canadian scientists may offer insight into mad cow disease
4. Emory researchers identify signaling protein for multiple myeloma
5. Human C-reactive protein regulates myeloma tumor cell growth and survival
6. Lowering Blood Protein Wont Help Kidney Patients
7. Blood protein detects lung cancer, even at earliest stage
8. Natural Protein Could Help Spot, Treat Liver Cancer
9. Heat shock proteins are co-opted for cancer
10. How adhesive protein causes malaria
11. Loss of gene leads to protein splicing and buildup of toxic proteins in neurons
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:7/21/2017)... ... July 21, 2017 , ... How physicians and athletic trainers ... say researchers presenting their work at the American Orthopaedic Society for Sports ... evaluating the patterns of change in concussion symptom presentation, diagnostic tools used and ...
(Date:7/20/2017)... ... 2017 , ... ChenMed , a leading provider of value-based care for ... as Richmond Chief Medical Officer. Dr. McCarter, formerly Associate Professor of Family ... of Ambulatory Services for the UVA Health System, brings 30 years of highly relevant ...
(Date:7/20/2017)... ... July 20, 2017 , ... ... IT operations analytics and application performance monitoring (APM) solutions, has expanded its ... services providers. , According to Peter Ohrenberger, sales director at Nastel, “We’ve ...
(Date:7/20/2017)... ... 20, 2017 , ... For individuals with extended hospital stays or who are ... such facilities are specially designed to accommodate patients with a wide range of ailments ... from Rochester, Ind., has invented the patent-pending PORTABLE ARM REST, a specially designed armrest ...
(Date:7/20/2017)... (PRWEB) , ... July 20, 2017 , ... Team Type ... access to medicine for everyone affected by diabetes, is teaming up with a Microsoft ... global event kicks off on July 24th. , “Team Type 1’s mission overlaps ...
Breaking Medicine News(10 mins):
(Date:7/21/2017)... , July 21, 2017 Did you know that PhRMA ... 2016? Or that combined spending on brand medicines, generics and the ... with brands accounting for just half of this (7 percent)? Or ... thirds of the world,s venture capital investments in high-growth biopharmaceutical startups? ... ...
(Date:7/19/2017)... RALEIGH, N.C. , July 19, 2017  Mako ... Veteran Affairs, and the Military Family Assistance Fund (MFA) ... Louisiana to visit with their families one ... the funding to coordinate the travel and logistics needed ... supporting our deployed soldiers and their families. We just ...
(Date:7/15/2017)... , July 15, 2017 Enterin Inc., a ... treat Parkinson,s disease (PD), today announced the completion of a ... investors New Ventures III, as well as the participation of ... absolutely thrilled to have the support of New Ventures III ... investors as validation of the potential of our platform technology ...
Breaking Medicine Technology: