Navigation Links
Research shows cell's inactive state is critical for effectiveness of cancer treatment
Date:1/9/2009

NEW YORK, January 9, 2009 A new study sheds light on a little understood biological process called quiescence, which enables blood-forming stem cells to exist in a dormant or inactive state in which they are not growing or dividing. According to the study's findings, researchers identified the genetic pathway used to maintain a cell's quiescence, a state that allows bone marrow cells to escape the lethal effects of standard cancer treatments.

Researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) found elevated levels of the tumor suppressor protein p53 in hematopoietic stem cells (HSCs) immature cells in the bone marrow that have the capacity to differentiate into all types of mature blood cells. They showed that when chemotherapy or radiation is delivered to a cell that lacks both p53 and a gene called MEF, the cell not only becomes less quiescent, but also becomes more susceptible to being killed. These findings are published in the January 9, 2009, issue of Cell Stem Cell.

"This is the first time that anyone has established that p53 has a role in defining a cell's state of quiescence. Furthermore, it is surprising that some cells that lose p53 can actually be killed more readily than those that have p53 intact," said the study's senior author, Stephen Nimer, MD, Chief of the Hematology Service and Member of the Molecular Pharmacology and Chemistry Program at MSKCC. "Our findings have important implications for developing therapeutic strategies that could eliminate quiescent cancer stem cells."

The study builds on previous research in which Dr. Nimer and colleagues first identified the MEF gene and showed its ability to control the state of quiescence of HSCs as well as its critical role in determining the sensitivity of normal bone marrow cells to chemotherapy and radiation. They have now identified p53 as the pathway that MEF utilizes to maintain this enhanced quiescence.

It is known that when a cell experiences DNA damage as a result of cancer treatment, p53 plays a critical role in guarding the genomic integrity of the cell by either triggering it to die or by causing cells to stop growing so they can repair their DNA successfully. However, p53 has additional functions during the process of blood cell formation in the body a process called hematopoiesis.

In the current study, investigators set out to determine whether the increased amount of p53 and enhanced expression of p53 target genes might contribute to the quiescence of cells and their ability to resist chemotherapy. They examined the function of p53 during hematopoiesis and found an important interdependency between p53 and its target gene, MEF, on HSC quiescence.

"Our findings suggest that by targeting those specific genes that control quiescence in cancer cells, we may enhance the anticancer effects of chemotherapy and radiotherapy, thereby promoting their effectiveness," said Dr. Nimer.

In addition, researchers identified two new targets of the p53 protein Necdin and Gfi-1 tumor growth suppressor genes that also regulate quiescence. Researchers lowered the expression of Necdin and Gfi-1 in hematopoietic stem cells lacking MEF and found a significant reduction in the quiescence of those cells. The results suggest that these p53 target genes are functionally responsible for the enhanced quiescence of HSCs in which MEF has been eliminated.


'/>"/>

Contact: Esther Napolitano
napolite@mskcc.org
212-639-3573
Memorial Sloan-Kettering Cancer Center
Source:Eurekalert

Related biology news :

1. Research shows skeleton to be endocrine organ
2. Newly created cancer stem cells could aid breast cancer research
3. Dominant cholesterol-metabolism ideas challenged by new research
4. Researchers identify proteins involved in new neurodegenerative syndrome
5. Texas researchers and educators head for Antarctica
6. MGH researchers describe new way to identify, evolve novel enzymes
7. University of Pennsylvania researchers develop formula to gauge risk of disease clusters
8. University of Oregon researcher finds that on waters surface, nitric acid is not so tough
9. U of MN researchers discover noninvasive diagnostic tool for brain diseases
10. U of Minnesota researchers discover noninvasive diagnostic tool for brain diseases
11. Story ideas from the Journal of Lipid Research
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/14/2017)... IBM ) is introducing several innovative partner startups at VivaTech ... startups and global businesses, taking place in Paris ... will showcase the solutions they have built with IBM Watson ... France is one of the most dynamic ... in the number of startups created between 2012 and 2015*, ...
(Date:5/6/2017)... SINGAPORE , May 5, 2017 ... has just announced a new breakthrough in biometric ... that exploits quantum mechanical properties to perform ... new smart semiconductor material created by Ram Group ... across finance, entertainment, transportation, supply chains and security. ...
(Date:4/17/2017)... , April 17, 2017 NXT-ID, Inc. ... company, announces the filing of its 2016 Annual Report on Form ... Exchange Commission. ... Form 10-K is available in the Investor Relations section of the ... on the SEC,s website at http://www.sec.gov . 2016 ...
Breaking Biology News(10 mins):
(Date:10/9/2017)... ... October 09, 2017 , ... At its national board meeting ... a professor in Harvard University’s Departments of Physics and Astronomy, has been selected for ... of the winning team for the 2015 Breakthrough Prize in Fundamental physics for the ...
(Date:10/9/2017)... ... October 09, 2017 , ... ... in the medical journal, Epilepsia, Brain Sentinel’s SPEAC® System which uses the ... in detecting generalized tonic-clonic seizures (GTCS) using surface electromyography (sEMG). The prospective ...
(Date:10/7/2017)... ... October 06, 2017 , ... ... genomic technologies, launched its ProxiMeta™ Hi-C metagenome deconvolution product, featuring the first ... accompanying cloud-based bioinformatics software to perform Hi-C metagenome deconvolution using their own ...
(Date:10/6/2017)... ... October 06, 2017 , ... The HealthTech Venture Network ... at their fourth annual Conference where founders, investors, innovative practitioners and collaborators are ... pitch competition showcasing early stage digital health and med tech companies. , This ...
Breaking Biology Technology: