Navigation Links
Tumor suppressor p53 prevents cancer progression in cells with missegregated chromosomes
Date:2/1/2010

Cells missegregate a chromosome approximately once every hundred divisions. But don't be too alarmed: new research in the Journal of Cell Biology shows that the tumor suppressor p53 limits the growth of cells with incorrect numbers of chromosomes and prevents their progression toward cancer. The study appears online February 1 (www.jcb.org).

Tumor cells tend to missegregate chromosomes at a particularly high frequency (a condition known as chromosomal instability, or CIN), which is probably why they are often aneuploid (i.e., they carry an abnormal number of chromosomes). In 2008, Sarah Thompson and Duane Compton, from Dartmouth Medical School, revealed that most CIN in tumor cells was caused by incorrect attachments between mitotic spindle microtubules and kinetochores, and that inducing misattachments in normal cells was sufficient to generate high rates of chromosome missegregation. There was a small but significant wrinkle to this story, however: normal, diploid cells stopped proliferating as soon as they gained or lost a chromosome, so they never converted into a cancer-like aneuploid cell line.

To investigate why normal cells stop proliferating when they missegregate their DNA, Thompson and Compton engineered a human cell line to carry a unique fluorescent mark on one of its chromosomes. This allowed them to identify and follow by live microscopy the cells that missegregated a chromosome.

The researchers induced missegregation and then looked for cells that had gained or lost a fluorescent mark within their genome. These cells failed to proliferate, and showed elevated levels of p53 and one of its transcriptional targets, the cell cycle inhibitor p21. Cells lacking p53 became aneuploid after induced missegregation, indicating that the p53 pathway normally serves to limit the propagation of cells with odd numbers of chromosomes.

How is p53 activated by chromosome missegregation? Thompson and Compton think that a change in chromosome number leads to an imbalance in gene expression, resulting in a stress response and cell cycle arrest that is vital to avoid cancer. "By combining loss of p53 with increased missegregation rates, we can convert a diploid cell into something . that looks like a tumor cell," says Compton. Furthermore, these aneuploid cells develop an inherent genomic instability reminiscent of genuine cancer cells, perhaps because imbalanced gene expression also causes disruptions to mitosis.

A recent study demonstrated that chromosome missegregation initiates tumorigenesis by causing cells to lose tumor suppressors like p53. "It's like a self-fulfilling prophecy," argues Compton. "If you missegregate a chromosome encoding p53, you make the cells deficient in p53, so they're able to propagate and missegregate more chromosomes."

There are circumstances in which nontumor cells tolerate aneuploidy just fine, but, in most cases, healthy cells keep a tight check on chromosome number. "I think it affects a lot of different pathways," says Compton. "The next question to ask is which pathways are sensitive to aneuploidy, and how do tumor cells overcome those problems?"


'/>"/>

Contact: Rita Sullivan
news@rupress.org
212-327-8603
Rockefeller University Press
Source:Eurekalert  

Related biology news :

1. Drug shows promise as new treatment for gut tumor
2. Nervous culprit found for Tassie devil facial tumor disease
3. Delivering medicine directly into a tumor
4. New understanding of how to prevent destruction of a tumor suppressor
5. Tiny RNA has big impact on lung cancer tumors
6. Discovery makes brain tumor cells more responsive to radiation
7. Tumor-attacking virus strikes with one-two punch
8. CSHL study shows that some malignant tumors can be shut down after all
9. Testicular tumors may explain why some diseases are more common in children of older fathers
10. Loss of tumor supressor gene essential to transforming benign nerve tumors into cancers
11. Trial of new treatment for advanced melanoma shows rapid shrinking of tumors
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Tumor suppressor p53 prevents cancer progression in cells with missegregated chromosomes
(Date:1/12/2017)... NEW YORK , Jan. 12, 2017  New research ... around the office of the future.  1,000 participants were simply ... last three months which we may consider standard issue.  Insights ... office of 2017 were also gathered from futurists and industry ... and Dr. James Canton .  Some ...
(Date:1/11/2017)... 11, 2017  Michael Johnson, co-founder of Visikol Inc. a company ... has been named to the elite "Forbes 30 Under 30" list ... 600 people in 20 fields nationwide to be recognized as a ... applicants were selected. ... He is currently a PhD candidate at Rutgers University. ...
(Date:1/6/2017)...  Delta ID Inc., a leader in consumer-grade iris ... at CESĀ® 2017. Delta ID has collaborated with Gentex ... use of iris scanning as a secure, reliable and ... a car, and as a way to elevate the ... Delta ID and Gentex will demonstrate (booth #7326 LVCC) ...
Breaking Biology News(10 mins):
(Date:1/20/2017)... ... January 20, 2017 , ... ... Surgery (LES®) Technologies, announced today the next evolution in spinal fusion, the ... platform). In contrast to the competition, SpineFrontier is focused on technique driven ...
(Date:1/19/2017)... , Jan. 19, 2017 /PRNewswire -- WuXi AppTec, ... open-access capability and technology platform, today announced that ... biology focused preclinical drug discovery contract research organization ... become a wholly-owned subsidiary of WuXi, and will ... and providing greater services. The acquisition will further ...
(Date:1/19/2017)... and GAITHERSBURG, Md. , ... PIP) and Altimmune, Inc., a privately-held immunotherapeutics company ... a definitive agreement for the merger of PharmAthene ... investors include Novartis Venture Fund, HealthCap, Truffle Capital ... a fully-integrated and diversified immunotherapeutics company with four ...
(Date:1/19/2017)... ... January 18, 2017 , ... LabRoots , the leading ... the world, was today awarded the "Best Science & Technology Social Networking Service ... and decided upon by a dedicated team of researchers and analysts. , The ...
Breaking Biology Technology: