Navigation Links
CSHL scientists discover how a tumor suppressor induces senescence and staves off cancer
Date:4/13/2010

Cold Spring Harbor, N.Y. A frequently mutated gene in human cancers is the reitnoblastoma (RB) gene, which controls a potent tumor suppression pathway. Mutations in the gene disable the vast and intricate RB pathway in virtually all tumor cells, leading to disturbances in a host of cellular functions and ultimately provoking cancer. But which of these functions is crucial for the gene's tumor-suppressing activity has been uncertain.

"We have now found that a key function of RB in suppressing cancer stems from its ability to induce cellular senescence, a stage of growth arrest in which cells no longer divide," explains Cold Spring Harbor Laboratory (CSHL) Professor and HHMI investigator Scott Lowe, Ph.D. His team's findings appear online on 13th April in the journal Cancer Cell.

RB's exact mode of activity has been difficult to tease out because it is part of a multigene family that includes two other members that are structurally very similar to RB and have highly overlapping functions. And yet, RB's activities appear to be a more vital part of cells' anti-cancer arsenal as compared to other RB family members, which are very rarely mutated in human cancers.

One of the cellular processes controlled by the RB family is cellular senescence, which is now known to act as a barrier against cancer. "So we hypothesized that the RB protein must exclusively target and control certain senescence-related proteins, which in turn must mediate its potent tumor- suppressive function," explains Lowe.

To investigate the relative effects of each RB family member on senescence, Lowe's team generated multiple short hairpin RNA (shRNA) molecules that specifically shut off individual RB family genes when introduced into human cells with intact RB networks. The team then switched on an oncogene in these cells, which normally triggers cells to cease dividing and enter the senescence mode as part of a failsafe mechanism that prevents cancer.

The team found that when RB alone was switched off, the cells could not efficiently undergo this process of oncogene-induced senescence. When these cells lost RB activity, they could not shut off DNA replication, began to replicate out of control and developed genomic instability. "These aberrant processes, when exacerbated by breakdowns in other control mechanisms, lead to the development of malignant tumors," says Agustin Chicas, Ph.D., a postdoctoral fellow working with Dr. Lowe and the lead investigator in the study.

Further investigations showed that a key target of RB is a gene called cyclin E1, which has been found to be overactive in many human tumors and is often associated with poor prognosis in patients. Its normal function is to spur DNA replication during the cell cycle and hence it is tightly suppressed by RB in senescent cells. The team showed that the loss of RB frees cyclin E1, thus allowing cells to escape senescence.

"Our team's findings suggest that the selective targeting of DNA replication genes during senescence represents one key activity of RB in tumor suppression," says Lowe.


'/>"/>

Contact: Hema Bashyam
bashyam@cshl.edu
516-367-6822
Cold Spring Harbor Laboratory
Source:Eurekalert

Related medicine news :

1. Scientists ID a protein that splices and dices genes
2. Breakthrough by Danish scientists in preventing maternal malaria
3. NIH scientists identify maternal and fetal genes that increase preterm birth risk
4. UM School of Medicine scientists find new malaria vaccine is safe and protective in children
5. Gladstone scientists identify target that may reduce complications of obesity
6. Scientists map out regulatory regions of genome, hot spots for diabetes genes
7. Doctors and Scientists Create New Society to Promote Non-Animal Toxicology Testing Methods
8. Scientists discover enzyme that cleans cancer cells
9. Scientists Decode Brain Cancer Cell Line
10. Scientists show how molecular switch helps pancreatic cancer beat drugs
11. Brain scientists extend map of fear memory formation
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:9/22/2017)... CA (PRWEB) , ... September 22, 2017 , ... ... to help you brush more effectively even on the go. Their electric toothbrushes ... gingivitis and gum inflammation, with UV sanitizing technology. Combining leading edge Enke technology ...
(Date:9/22/2017)... ... September 22, 2017 , ... Global Lyme Alliance ... research, education and awareness, today announced the appointment of Timothy J. Sellati, Ph.D. ... Sellati has more than 20 years of research experience with Lyme and other ...
(Date:9/21/2017)... ... 21, 2017 , ... The American Addiction Treatment Association (AATA) ... in the addiction treatment industry entitled: Special Investigations Unit (SIU) – What ... state and federal governments are increasingly scrutinizing the addiction treatment industry for fraudulent ...
(Date:9/21/2017)... ... , ... In addition to sticking with the new years ... and use natural alternatives for all house cleaning products, disinfectants, respiratory relief, and ... the new line of essential oils, are all 100% organic and natural. , ...
(Date:9/21/2017)... RICHMOND, Va. (PRWEB) , ... September 21, 2017 ... ... Richmond with a different approach to addiction recovery at a time when Virginia ... 1,420 deaths resulting from drug overdose, a staggering increase of 38 percent from ...
Breaking Medicine News(10 mins):
(Date:9/6/2017)...  Medical professionals are expected to continuously ... their patients. Medical simulations offer clinicians the ... Simulation provides a safe method for teaching ... refine techniques and build confidence, without putting ... such as augmented reality, will now provide ...
(Date:9/5/2017)... 5, 2017  Xyntek Inc. has announced another milestone in their continued growth ... to meet the growing demands of customer engagements regionally.  ... Xyntek's new Midwest office is located at 318 West Adams Street, Suite ... Xyntek's ... ...
(Date:9/1/2017)... , Sept. 1, 2017  Explorers Like Us ( https://explorerslikeus.com/ ... greatest aural experiences — and deliver these experiences as part ... help people feel and heal better. ... While nothing beats a walk, jog ... your mind, Life Environments™ is the next best thing when ...
Breaking Medicine Technology: