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:5/20/2016)... 20, 2016  VoiceIt is excited to announce ... By working together, VoiceIt and VoicePass ... and VoicePass take slightly different approaches to voice ... security and usability. ... new partnership. "This marketing and technology ...
(Date:5/12/2016)... , May 12, 2016 WearablesResearch.com ... just published the overview results from the Q1 wave ... the recent wave was consumers, receptivity to a program ... data with a health insurance company. "We ... to share," says Michael LaColla , CEO of ...
(Date:5/3/2016)... May 3, 2016  Neurotechnology, a provider of ... MegaMatcher Automated Biometric Identification System (ABIS) , a ... projects. MegaMatcher ABIS can process multiple complex biometric ... combination of fingerprint, face or iris biometrics. It ... and MegaMatcher Accelerator , which have ...
Breaking Biology News(10 mins):
(Date:5/31/2016)... ... May 31, 2016 , ... Cubresa Inc. ... announced that their compact PET scanner called NuPET™ for simultaneous preclinical ... the University of Arizona (UA). , PET and MRI are complementary imaging methods ...
(Date:5/27/2016)... ... ... Weeks after hosting a carpal tunnel syndrome workshop with Dr. Oz on ... of the Fitzmaurice Hand Institute, has announced the addition of MRI diagnostic imaging services ... only 1 of about 3 currently available in the United States. Developed specifically for ...
(Date:5/27/2016)... and READING, England ... Indegene ( http://www.indegene.com ), ein ... Lösungen für die Life-Science-Branche, Pharmaunternehmen und Gesundheitsorganisationen, ... weltweiter Anbieter von innovativen wissenschaftlichen Support-Services für ... Starts von IntraScience heute den Ausbau ihrer ...
(Date:5/26/2016)... New Jersey and READING, ... Indegene ( http://www.indegene.com ), a leading ... to life science, pharmaceutical and healthcare organisations and ... of innovative scientific support throughout the product lifecycle, ... with the launch of IntraScience.      ...
Breaking Biology Technology: