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:3/23/2017)... Research and Markets has announced the addition of the "Global ... 2025" report to their offering. ... The Global Vehicle Anti-Theft System Market is ... next decade to reach approximately $14.21 billion by 2025. ... all the given segments on global as well as regional levels ...
(Date:3/22/2017)... , March 21, 2017 Vigilant ... company serving law enforcement agencies, announced today the appointment ... as director of public safety business development. ... law enforcement experience, including a focus on the aviation ... his most recent position, Mr. Sheridan served as the ...
(Date:3/16/2017)... 2017 CeBIT 2017 - Against identity fraud with DERMALOG solutions "Made ... ... Used combined in one project, multi-biometric solutions provide a crucial contribution against identity ... Used combined in one project, multi-biometric ... ...
Breaking Biology News(10 mins):
(Date:6/22/2017)... Ca (PRWEB) , ... June 22, 2017 , ... The ... It took 20 years until the first data on cross-contamination of human cell lines ... has been an increasing issue in cell culture labs and is associated with dramatic ...
(Date:6/22/2017)... ... 22, 2017 , ... Charm Sciences, Inc. is pleased to announce that its ... be appropriate as a screening test at dairies and farms for raw commingled cow ... the Charm EZ Lite system. These systems are a combination incubator and reader in ...
(Date:6/20/2017)... Fort Lauderdale, Florida (PRWEB) , ... June 20, 2017 , ... ... and commitment in men. While researching her latest book, Men Chase, Women Choose: The ... that showed that love has a physiological effect on men. ”The logical next step, ...
(Date:6/20/2017)... , June 20, 2017  Kibow Biotech Inc., a ... announce the issuance of a new patent covering a ... by the U.S. Patent and Trademark Office on May ... of the Buzz of Bio award in 2014 in ... to developing non-drug approaches to chronic disease. Renadyl™, the ...
Breaking Biology Technology: