Navigation Links
Reactivated Genes Cause Tumors to Shrink (or) Disappear

Many cancers arise due to defects in genes that normally suppress tumor growth. Now, for the first time, //MIT researchers have shown that re-activating one of those genes in mice can cause tumors to shrink or disappear.

The study offers evidence that the tumor suppressor gene p53 is a promising target for human cancer drugs.

"If we can find drugs that restore p53 function in human tumors in which this pathway is blocked, they may be effective cancer treatments," said David Kirsch of MIT's Center for Cancer Research and Harvard Medical School, one of the lead co-authors of the paper.

The study will be published in the Jan. 24 online edition of Nature. It was conducted in the laboratory of Tyler Jacks, director of the Center for Cancer Research, the David H. Koch Professor of Biology and a Howard Hughes Medical Institute investigator.

P53 has long been known to play a critical role in the development of many tumors-it is mutated in more than 50 percent of human cancers. Researchers have identified a few compounds that restore p53 function, but until now, it has not been known whether such activity would actually reverse tumor growth in primary tumors.

The new MIT study shows that re-activating p53 in mouse tumors dramatically reduces the size of the tumors, in some cases by 100 percent.

"This study provides critical genetic evidence that continuous repression of a tumor suppressor gene is required for a tumor to survive," said Andrea Ventura, an Italian postdoctoral associate in the Center for Cancer Research and first author of the paper.

In normal cells, p53 controls the cell cycle. In other words, when functioning properly, it activates DNA repair mechanisms and prevents cells with damaged DNA from dividing. If DNA damage is irreparable, p53 induces the cell to destroy itself by undergoing apoptosis, or programmed cell death.

When p53 is turned off by mutation or dele tion, cells are much more likely to become cancerous, because they will divide uncontrollably even when DNA is damaged.

In this study, the researchers used engineered mice that had the gene for p53 turned off. But, they also included a genetic "switch" that allowed the researchers to turn p53 back on after tumors developed.

Once the switch was activated, p53 appeared in the tumor cells and the majority of the tumors shrank between 40 and 100 percent.

The researchers looked at two different types of cancer-lymphomas and sarcomas. In lymphomas, or cancers of the white blood cells, the cancer cells underwent apoptosis within 1 or 2 days of the p53 reactivation.

In contrast, sarcomas (which affect connective tissues) did not undergo apoptosis but went into a state of senescence, or no growth. Those tumors took longer to shrink but the senescent tumor cells were eventually cleared away.

The researchers are not sure why these two cancers are affected in different ways, but they have started trying to figure it out by identifying the other genes that are activated in each type of tumor when p53 turns back on.

The study also revealed that turning on p53 has no damaging effects in normal cells. The researchers had worried that p53 would kill normal cells because it had never been expressed in those cells.

"This means you can design drugs that restore p53 and you don't have to worry too much about toxic side effects," said Ventura.

Possible therapeutic approaches to turn on p53 in human cancer cells include small molecules that restore mutated p53 proteins to a functional state, as well as gene therapy techniques that introduce a new copy of the p53 gene into tumor cells. One class of potential drugs now under investigation, known as nutlins, acts by interfering with MDM2, an enzyme that keeps p53 levels low.

In follow-up studies, the MIT researchers are looking at oth er types of cancer, such as epithelial (skin) cancer, in their mouse model, and they plan to see if the same approach will also work for tumor suppressors other than p53.



Source-Eurekalert
SRI
'"/>




Related medicine news :

1. New Way to "See" Genes, Evaluate Effectiveness of Gene Therapies Discovered
2. Genes for lung disease
3. Genesis of SUPAC
4. Genes for Vision discovered
5. Genes Found To Help Leukemia Treatment
6. Cardiac Valve Disease Linked To Genes
7. Genes Linked To Cigarette Addiction
8. Genes from saliva may predict oral and breast cancer
9. Genes More Important Than Exercise for Bad Cholesterol
10. Genes responsible for social behavior of us
11. Genes to Extend Longevity Discovered
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/18/2017)... Dallas, Texas (PRWEB) , ... February 17, 2017 , ... ... Arden Moore’s “Oh Behave” Show on the Pet Life Radio network. The episode, ... explores a number of topics including: what factors led to Park Cities Pet Sitter’s ...
(Date:2/17/2017)... CA (PRWEB) , ... February 17, 2017 , ... ... focus on foundational and sustainable systems change designed to further positively impact the ... “The Board of Trustees has long considered it our duty to seriously consider ...
(Date:2/17/2017)... ... February 17, 2017 , ... Corrective ... Warning Letter, **An FDAnews Webinar**, Feb. 23, 2017 — 1:30 p.m. – 3:00 ... corrective action (CA) and preventive action (PA)? , The methods share techniques and ...
(Date:2/17/2017)... ... February 17, 2017 , ... Pharmica Consulting attended CHI's ... facets of clinical trial planning and management. Pharmica discussed the importance of effective ... addition, attendees stopping by Pharmica’s booth were able to demo its cloud-based ...
(Date:2/17/2017)... ... 2017 , ... The Mason Pasquin Agency, a Virginia-based firm ... in and around the Hampton Roads metropolitan region, is joining the local nonprofit ... violence. , There are multiple categories of domestic violence – physical abuse is ...
Breaking Medicine News(10 mins):
(Date:2/16/2017)... DaVita Inc. (NYSE: DVA ) today ... 2016. Net income attributable to DaVita Inc. ... $158 million, or $0.80 per share and $880 million, or ... attributable to DaVita Inc. for the quarter and year ended ... $192 million, or $0.98 per share, and $789 million, or ...
(Date:2/16/2017)... -- Newly published research from the CVS Health (NYSE: ... private retailer can play in restricting access to tobacco ... in the American Journal of Public Health , ... all CVS Pharmacy stores reduced the number of cigarette ... impact on those who bought cigarettes exclusively at CVS ...
(Date:2/16/2017)... 16, 2017  Prescription pain medications provided by "physicians ... necessary for long-term opioid use to take hold," according ... edition of The New England Journal of ... more patients in acute pain than in almost any ... FACEP, president of the American College of Emergency Physicians. ...
Breaking Medicine Technology: