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:5/26/2017)... ... , ... “When the Stars Lead Home”: a poignant story of loss, determination, ... Weigel Douglas, an avid reader who lives in the Pacific Northwest with her husband, ... Hills Adventure Camp. She couldn’t be more grateful. , Twelve-year old Tizzy could not ...
(Date:5/26/2017)... ... May 26, 2017 , ... “Cactus Jack: Against All ... so many others. “Cactus Jack: Against All Odds” is the creation of published ... D. Hubbard is married to Jack Carlisle’s third child Jane. Walter. Walter and ...
(Date:5/24/2017)... York (PRWEB) , ... May 24, 2017 , ... Dr. ... vascular surgery in New York City. He is known for his distinguished expertise ... in vascular surgery, Dr. Benvenisty holds sub-specialty training in treating renovascular disease and ...
(Date:5/24/2017)... ... May 24, 2017 , ... Dr. Manju R. Kejriwal, a ... orthodontics, with or without a referral. Dr. Kejriwal understands the emotional and financial ... clear braces in Cincinnati, OH. Patients no longer need to feel the esthetic effects ...
(Date:5/24/2017)... , ... May 24, 2017 , ... ... completed Course II of the HP3 (High-Performance Periodontal Practice) continuing education (CE) series. ... the latest advancements in his field by attending numerous CE courses each year. ...
Breaking Medicine News(10 mins):
(Date:5/22/2017)... May 22, 2017  As the specialty pharmacy ... continue to make the revolutionary shift from volume-based ... for ensuring positive patient outcomes and shaping the ... shifting focus away from clinical trials and toward ... long-term specialty drug therapy utilization in precise patient ...
(Date:5/15/2017)... Enterin Inc., a privately-held CNS pharmaceutical company based ... to treat Parkinson,s disease (PD), has enrolled the first patient ... randomized, controlled, multicenter study involving patients with PD and taking ... over a 9-to-12-month period. The first stage is open label ... Participating sites include Denver , ...
(Date:5/10/2017)... , May 10, 2017 Global Health ... Latin America , published its 2017 ranking ... ranking is based on extensive data analysis from GHI,s ... largest hospitals database for the region. The GHI database covers ... , offering more than 130 data points for each institution ...
Breaking Medicine Technology: